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Assessment of child's dental anxiety/fear and stress during dental treatment: a systematic review by CEDACORE

Abstract:

There is a lack of evidence on the correlation between salivary biomarkers and subjective measures of dental fear and anxiety in children. This systematic review aimed to retrieve the scientific evidence comparing the results of dental anxiety measured by salivary biomarkers with patient-reported outcomes in pediatric dental setting. The PECOS was as follows: population: pediatric patients aged ≤ 18 years; exposure: patient-reported outcome measures, such as scales and/or questionnaires; comparator: salivary biomarkers; outcome: anxiety, fear, phobia or stress during dental treatment; study design: observational studies or controlled trials. Electronic searches were conducted in PubMed, Scopus, Web of Science, and Ovid databases. Studies that compared scales/questionnaires and salivary biomarkers for the evaluation of dental anxiety, fear, and stress in children/adolescents during dental treatment were included. Certainty of evidence was assessed with GRADE. Risk of bias of the included studies was assessed with the Cochrane tool or the University of Adelaide tool. From the 314 studies identified, eight were included. Participants’ age ranged from three to 13 years. The most used salivary biomarkers and instruments were cortisol and the Dental Subscale of the Children's Fear Survey Schedule, respectively. Most studies showed a weak correlation between objective and subjective measures. The main issues regarding bias were on allocation concealment, blinding of assessors, follow up, and exposure assessment. Certainty of evidence was low/very low. Evidence of salivary biomarkers and patient-reported outcome measures to investigate anxiety, fear and stress in children during in the dental environment is limited. There was no correlation between subjective and objective measures in almost all included studies.

Keywords:
Dental Care for Children; Hydrocortisone; Alpha-Amylases; Chromogranin A; Surveys and Questionnaires

Introduction

Measurement of dental anxiety, fear, and stress in children is largely based on observed behavior rating scales or questionnaires.11 Porritt J, Buchanan H, Hall M, Gilchrist F, Marshman Z. Assessing children's dental anxiety: a systematic review of current measures. Community Dent Oral Epidemiol. 2013 Apr;41(2):130-42. https://doi.org/10.1111/j.1600-0528.2012.00740.x
https://doi.org/10.1111/j.1600-0528.2012...
However, the accuracy of such scales and questionnaires in determining what the child actually feels during dental treatments is limited due to their subjectivity, the need for a skilled examiner,11 Porritt J, Buchanan H, Hall M, Gilchrist F, Marshman Z. Assessing children's dental anxiety: a systematic review of current measures. Community Dent Oral Epidemiol. 2013 Apr;41(2):130-42. https://doi.org/10.1111/j.1600-0528.2012.00740.x
https://doi.org/10.1111/j.1600-0528.2012...
and the need for training in the use of the tool.22 Lochary ME, Wilson S, Griffen AL, Coury DL. Temperament as a predictor of behavior for conscious sedation in dentistry. Pediatr Dent. 1993 Sep-Oct;15(5):348-52.44 Hosey MT, Blinkhorn AS. An evaluation of four methods of assessing the behaviour of anxious child dental patients. Int J Paediatr Dent. 1995 Jun;5(2):87-95. https://doi.org/10.1111/j.1365-263X.1995.tb00170.x
https://doi.org/10.1111/j.1365-263X.1995...
Another method of measuring the stress of a child during dental treatment is through saliva. Under certain conditions such as dental treatment, the allostatic systems become deregulated and alterations in saliva occur.55 Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012 Apr;106(1):29-39. https://doi.org/10.1016/j.physbeh.2011.08.019
https://doi.org/10.1016/j.physbeh.2011.0...
Heart rate, blood pressure, electrodermal activity, and salivary cortisol are examples of objective measures to assess dental anxiety/fear/stress in children. Studies have questioned the usefulness of heart rate, blood pressure, and electrodermal activity to investigate anxiety/fear/stress.66 Góes MP, Domingues MC, Couto G, Barreira AK. Anxiety, fear and vital signs of the child signs of the child patients. Odontol Clín Cient. 2010;9(1):39-44. Conversely, salivary components as biomarkers of physiological characteristics have been widely used in dentistry to assess caries risk, salivary gland function,77 Castagnola M, Picciotti PM, Messana I, Fanali C, Fiorita A, Cabras T, et al. Potential applications of human saliva as diagnostic fluid. Acta Otorhinolaryngol Ital. 2011 Dec;31(6):347-57. and stress in children during dental treatments by examining salivary cortisol.33 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 randomised controlled trial. Braz Oral Res. 2015;29(1):S1806-83242015000100305. https://doi.org/10.1590/1807-3107BOR-2015.vol29.0125
https://doi.org/10.1590/1807-3107BOR-201...
,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,99 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;16(1):74. https://doi.org/10.1186/s12903-016-0273-1
https://doi.org/10.1186/s12903-016-0273-...

Both salivary cortisol and subjective (patient-reported outcome measures - PROMs) methods such as scales and questionnaires have been used to evaluate dental anxiety/fear/stress in children.1010 Guinot Jimeno F, Yuste Bielsa S, Cuadros Fernández C, Lorente Rodríguez AI, Mercadé Bellido M. Objective and subjective measures for assessing anxiety in paediatric dental patients. Eur J Paediatr Dent. 2011 Dec;12(4):239-44. However, despite the large number of assessment instruments, no systematic attempt has been made to compile the studies comparing objective and subjective measures. Such information could be helpful in choosing the tool used evaluate children's dental anxiety/fear/stress during dental appointments. Therefore, the aim of this systematic review was to compare salivary biomarkers with patient-reported outcome measures to assess dental fear or anxiety in children.

Methodology

Protocol and registration

This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.1111 Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009 Oct;62(10):1006-12. https://doi.org/10.1016/j.jclinepi.2009.06.005
https://doi.org/10.1016/j.jclinepi.2009....
A protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO), under registration number CRD42018108929.

Eligibility criteria

The eligibility criteria were chosen using the PECOS (population, exposure, comparator, outcomes and study design) strategy: a) population: pediatric patients aged up to 18 years; b) exposure: patient-reported outcomes measures, such as scales and/or questionnaires; c) comparator: salivary biomarkers; d) outcome: dental anxiety, fear, phobia or stress during dental treatment; and e) study design: observational studies (cross-sectional, cohort or case-control studies) or randomized controlled trials (RCT). No restrictions were placed on language or publication date. Meeting abstracts, editorials, literature reviews, and letters to the editor were excluded. Moreover, studies were not excluded based on their methodological quality.

Information sources

Computerized searches were conducted on May 2020 across four electronic databases: PubMed (National Library of Medicine), Scopus (Elsevier), Web of Science (Thomson Reuters), and Ovid (Wolters Kluwer). The reference lists of the included articles were also screened for the identification of references that might not have been retrieved in the searches in the electronic databases. Finally, a search through Google Scholar limited to the first 300 hits was carried out. Duplicates were removed upon identification. References were managed using EndNote software (EndNoteTM, Clarivate Analytics, Toronto, Canada).

Search

Keywords and Boolean operators were selected and combined. The following search strategy was used in all databases: pediatric dentistry OR pediatric dentistry OR child OR children OR adolescent OR adolescents OR toddler OR teenager OR infant AND dental stress OR dental anxiety OR dental phobia OR dental fear OR odontophobia AND saliva biomarker OR salivary biomarker OR saliva biomarkers OR salivary biomarkers OR biomarker OR biological markers OR cortisol OR alpha-amylase OR alpha amylase OR nitric oxide OR melatonin OR immunoglobulin-A OR immunoglobulin A OR Ig-A OR Ig A OR chromogranin A.

Study selection

Study selection was performed by two authors, who worked independently. Titles/abstracts were assessed. The studies that met the eligibility criteria were included. If the titles or abstracts had insufficient information for a decision on inclusion or exclusion, the full text was retrieved for evaluation using the same eligibility criteria. Full texts that fulfilled the eligibility criteria were also included.

Data extraction

For each included study, the following data were extracted: first author's last name and year of publication, sampling (number of groups and description of groups as well as participants’ sex and age), description of the methods used for the evaluation of patient-reported outcomes and salivary biomarkers, dental procedures and evaluation times, statistical analysis used, and main results.

Risk of bias in individual studies

Evaluation of the risk of bias of included studies was performed by two review authors independently. The risk of bias in randomized clinical trials was assessed by means of the Cochrane tool. The following items were assessed: sequence generation, allocation concealment, blinding of participants/personnel, blinding of outcome assessment, incomplete outcome data, selective reporting of outcome, and other sources of bias. According to this tool, for each item in the study the risk of bias is classified as of low-quality, high-quality, or unclear.1212 Higgins JP, Green S, eds. Cochrane handbook for systematic reviews of interventions version 5.1.0. S. l.: The Cochrane Collaboration; 2011.

The risk of bias in cross-sectional studies was evaluated by means of the University of Adelaide tool. The following items were evaluated: clear description of criteria for inclusion in the sample, detailed description of subjects and setting, valid and reliable exposure measurement, objective and standard criteria for the condition measurement, identification of confounding factors, statement on strategies to deal with confounding factors, valid and reliable way for outcome measurement, and use of appropriate statistical analysis. For each item, the response could be yes, if the article had fulfilled the requirements for that item (low risk of bias) and no, if the article had not fulfilled the requirements for that item (high risk of bias). Unclear risk of bias is also an option.1313 The Joanna Briggs Institute. Joanna Briggs Institute Reviewers’ Manual. Adelaide: The Joanna Briggs Institute; 2011.

The risk of bias in the follow-up study was assessed using the University of Adelaide tool. This tool allows for the evaluation of the following aspects: whether exposure was measured in a similar manner to assign people to both the exposed and unexposed groups, whether exposure was measured in a valid and reliable way, whether confounding factors were identified, whether strategies for dealing with confounding factors were stated, whether outcomes were measured in a valid and reliable manner, whether follow-up time was specified and was long enough for outcomes to occur, whether follow-up was complete (if not, the reasons for loss to follow up were described and explored), whether strategies to address incomplete follow up were used, and if appropriate statistical analysis was used. For each item, the response could be yes, if the article had fulfilled the requirements for that item (low risk of bias) and no, if the article had not fulfilled the requirements for that item (high risk of bias). Unclear risk of bias was also an option.1313 The Joanna Briggs Institute. Joanna Briggs Institute Reviewers’ Manual. Adelaide: The Joanna Briggs Institute; 2011.

Assessment of the certainty of the evidence

The certainty of the evidence was judged according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. GRADE enables the assessment of the quality of the body of evidence based on the evaluation of the following parameters: study design, risk of bias, imprecision, inconsistency, indirectness, and other factors, such as publication bias.1414 Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004 Jun;328(7454):1490. https://doi.org/10.1136/bmj.328.7454.1490
https://doi.org/10.1136/bmj.328.7454.149...

Summary measures

The results regarding the comparison between salivary biomarkers and patient-reported outcome measures were provided with medians, quartiles, means, standard deviations, values of correlation coefficient (rho - Spearman correlation; r – Pearson correlation), and p-values.

Results

Study selection

A total of 314 references were identified. After the removal of 96 duplicates, 218 remained. Among them, 178 studies were excluded after the screening process. The main reasons for exclusion were articles not addressing issues related to salivary biomarkers and/or patient-reported outcome measures (n = 140), no comparison between salivary biomarkers and patient-reported outcome measures (n = 23), and other reasons, such as age, type of study, and context (n = 15). Among the 40 potentially eligible studies, 32 were excluded after full-text analysis. Thus, eight studies were included in this systematic review, five of which were cross-sectional studies,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
two were prospective cohort studies,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
and one was a randomized clinical trial.2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
Figure shows the search process and reasons for exclusion of references after full-text evaluation.

Figure 1
Flow diagram of the study steps.

Study characteristics

The included studies were published in English between 2007 and 2019 and were conducted in Greece,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
Japan,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
Sweden,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
India,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
, 2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
Turkey,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
and Saudi Arabia.2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
The sample size of the studies ranged from 201818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
to 151 pediatric patients.2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
The age of participants ranged from three to 13 years. In three studies, the respondents were not the children, but the parents/caregiver1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
or the dentist.2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....

The most used salivary biomarkers were cortisol (n = 6 studies),88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
followed by alpha amylase (n = 4),88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
and chromogranin A (n = 2).1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
No other biomarker was found. The saliva samples were collected at predetermined times, and in almost all studies samples were collected before, during, and/or after the dental intervention.88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....

These salivary biomarkers were compared with different instruments used to measure dental fear and dental anxiety in children. Dental fear was measured with the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS).88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
Dental anxiety was evaluated using the Corah Dental Anxiety Scale (CDAS)1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
, the Venham Clinical Anxiety Scale (VCAS),2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
and the Facial Image Scale (FIS).1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
In all included studies, these instruments were completed before the procedure.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
In two studies, the instruments were also applied after the intervention.1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....

In almost all studies, some procedures, such as clinical examination,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
prophylaxis,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8. restorations,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
radiographs,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
exposure to the noise of caries removal,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
and other non-invasive dental treatments (orthodontic treatment, topical fluoride application, pit and fissures sealants)1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8. were performed. In one study, the dental procedure that was performed was not specified. In this study, the authors stated that they recorded whether or not the dental treatment was successfully completed.2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
In two studies, children underwent restoration and extraction, pulpectomy, or pulpotomy.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
These procedures were performed under sedation2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
or general anesthesia.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
Study characteristics are described in Table 1.

Table 1
Characteristics and results of the included studies.

Risk of bias in included studies

The results of the risk of bias assessment of the randomized clinical trial2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
are provided in Table 2. The main issues regarding unclear risk of bias was for allocation concealment and blinding of assessors. For the longitudinal studies,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
a high risk of bias was found for follow up, given the lack of information that would allow the reader to decide whether or not the follow up had been completed and whether or not strategies to address incomplete follow up had been used (Table 3). In four cross-sectional studies, the item evaluating whether the exposure had been measured in a valid and reliable way presented an unclear risk of bias1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
or a high risk of bias1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
, 1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
(Table 4). The level of evidence was very low/low, given the data imprecision (Table 5).

Table 2
Quality assessment of the randomized clinical trial.
Table 3
Quality assessment of the follow-up study.
Table 4
Quality assessment of the cross-sectional studies.
Table 5
Assessment of the certainty of the evidence with GRADE.

Synthesis of results

Five studies compared a (trait) dental fear subjective measure (CFSS-DS) with a salivary biomarker, such as alpha amylase,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
cortisol,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
alpha amylase:cortisol ratio88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
and chromogranin A.1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
The CFSS-DS22 Lochary ME, Wilson S, Griffen AL, Coury DL. Temperament as a predictor of behavior for conscious sedation in dentistry. Pediatr Dent. 1993 Sep-Oct;15(5):348-52. questionnaire measures fear and anxiety and identifies their causes. The scale consists of 15 items related to various aspects of dental treatment. Scores below 31 indicate low anxiety, scores between 31 and 38 denote moderate anxiety, and scores higher than 38 indicate high anxiety regarding dental treatment.2323 Lalić M, Aleksić E, Milić J, Malešević A, Jovičić B. Reliability and validity of the Serbian version of Children's Dental Fear Questionnaire. Vojnosanit Pregl. 2015 Jul;72(7):602-7. https://doi.org/10.2298/VSP140209036LPMID:26364453
https://doi.org/10.2298/VSP140209036LPMI...

The pre-treatment median salivary cortisol, alpha amylase, and chromogranin A levels were significantly higher in patients with low CFSS-DS responded by parent (between 15 and 31) compared with those with moderate (between 32 and 39) and high scores (higher than 39) (p = 0.046).1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
Conversely, no difference was observed between individuals with increased and decreased alpha amylase regarding the CFSS-DS mean score (p = 0.19).1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8. The CFSS-DS score presented a weak negative correlation with the alpha amylase:cortisol ratio shortly after dental treatment (rho = -0.24). The CFSS-DS score presented a weak negative correlation with alpha amylase:cortisol ratio before dental treatment (rho = -0.15) and a weak positive correlation between 7 and 14 days after treatment at the recall visit (rho=0.02).88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
Another study demonstrated that the levels of salivary alpha-amylase and salivary cortisol three months and one year after dental treatment had a significant association with the level of dental fear (p = 0.029 and p = 0.000, respectively), confirming that phobic patients had the highest levels of salivary amylase and salivary cortisol.2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
There was no correlation between CFSS-DS responded by child/parents and change in chromogranin A level during the exposure to noise of an air turbine in preschool children (rho = 0.00) or schoolchildren (rho = 0.00),1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
but since CFSS-DS is a dental fear (trait) measure, this change was not expected.

Six studies compared subjective measures of dental anxiety, such as the VCAS,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
the CDAS1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
and the FIS1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
with salivary biomarkers, such as cortisol,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
alpha amylase and chromogranin A.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
The VCAS is a global scale, which was developed for the behavioral assessment of children during dental treatment. The assessment is done over a period of time and the predominant behavior of the child is noted at the end of the observation period.2424 Venham LL, Gaulin-Kremer E, Munster E, Bengston-Audia D, Cohan J. Interval rating scales for children's dental anxiety and uncooperative behavior. Pediatr Dent. 1980 Sep;2(3):195-202. The scale has six scores with more detailed descriptions of behaviors. The higher scores of the scale are representative of worse behaviors.2424 Venham LL, Gaulin-Kremer E, Munster E, Bengston-Audia D, Cohan J. Interval rating scales for children's dental anxiety and uncooperative behavior. Pediatr Dent. 1980 Sep;2(3):195-202. The reduction in the VCAS score according to pediatric dentistry presented a weak positive correlation with the change in salivary cortisol level in children sedated with intranasal midazolam (rho = 0.213) and with sublingual midazolam (rho = 0.265).2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....

No difference was observed regarding the mean salivary cortisol level among individuals with different levels of anxiety (low, moderate, high and severe) according to the CDAS (p = 0.214).1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
On the other hand, CDAS2525 Corah NL. Development of a dental anxiety scale. J Dent Res. 1969 Jul-Aug;48(4):596. https://doi.org/10.1177/00220345690480041801
https://doi.org/10.1177/0022034569048004...
contains questions about anxiety regarding dental treatment. It consists of four questions, specifically related to aspects of dental care, with five answer options. Only one answer must be selected, and each answer has a score between one and five. A total score ranging from 4 to 20 is achieved when adding the item scores. Scores below 12 indicate low anxiety, between 12 and 14, moderate anxiety, and greater than 14, high dental anxiety.2626 Corah NL, Gale EN, Illig SJ. Assessment of a dental anxiety scale. J Am Dent Assoc. 1978 Nov;97(5):816-9. https://doi.org/10.14219/jada.archive.1978.0394
https://doi.org/10.14219/jada.archive.19...
Conversely, another study, in which the CDAS was compared with cortisol, showed a positive correlation both in children with attention deficit hyperactivity disorder (r=0.54) and in children without this disorder (r = 0.28).1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...

No strong correlations were observed between salivary biomarkers and FIS scores.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
The FIS is a scale used to assess children's self-report dental anxiety according to.2727 Buchanan H, Niven N. Validation of a Facial Image Scale to assess child dental anxiety. Int J Paediatr Dent. 2002 Jan;12(1):47-52. This scale comprises a row of five faces ranging from “very happy” to “very unhappy”. All faces are scored by assigning a value of 1 to the happiest face and 5 to the saddest face. It is a simple and easy-to-apply scale, in which children are asked to indicated which face they recognized themselves most at the moment before being referred to the dental office.2727 Buchanan H, Niven N. Validation of a Facial Image Scale to assess child dental anxiety. Int J Paediatr Dent. 2002 Jan;12(1):47-52. The results of the included studies are described in Table 1.

Assessment of the certainty of the evidence

Two assessments were performed to compare salivary biomarkers and patient-reported outcome measures for evaluating dental fear or dental anxiety in children. In one assessment, seven observational studies were incorporated. In the second assessment, the randomized trial was incorporated. In both evaluations, there were very serious concerns regarding imprecision and the certainty of the evidence was either very low or low.

Discussion

This systematic review compared salivary biomarkers and patient-reported outcomes for the evaluation of dental fear or dental anxiety in children and found that the correlation between the two measures is limited in almost all included studies. This could be explained by methodological differences, as substantial heterogeneity was found among studies, especially a wide age range and differences in the dental procedures.

Scales and questionnaires assess dental fear and anxiety in several ways; some studies evaluated state dental fear and anxiety, by means of the VPT and FIS, and others evaluated trait dental fear and anxiety, such as using the CFSS-DS. Similarly, there was no child-, parent-, or observer-reported measure that could be used as a standard to compare with salivary biomarkers. Moreover, among the eight included studies, only one was a randomized clinical trial,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
which also limits the evaluation of the quality of evidence from the retrieved studies. Despite the low risk of bias presented in this randomized clinical trial study,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
the longitudinal studies88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
did not provide information that would allow the reader to decide whether or not follow-up had been complete or if strategies had been in place to deal with incomplete follow-up. In four cross-sectional studies,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
there was unclear or high risk of bias regarding whether the exposure was approached in a valid and reliable manner, suggesting caution during the interpretation of the results.

Nonetheless, there is no question that salivary biomarkers and psychometric indices are important in providing an objective approach for measuring children's physiological reactions and for the subjective assessment of children's dental fear/dental anxiety, respectively. The combination of both types of measures allows a better understanding of dental anxiety and dental fear in children, which contributes to the adequate management of oral health issues by the pediatric dentist. In clinical practice, children's self-report would better reflect their subjective feelings regarding the dental setting. Therefore, especially when salivary tests are not available, the busy clinician may use questionnaires to assess dental fear and anxiety, such as CFSS-DS, Modified Dental Anxiety Scale, CDAS,1010 Guinot Jimeno F, Yuste Bielsa S, Cuadros Fernández C, Lorente Rodríguez AI, Mercadé Bellido M. Objective and subjective measures for assessing anxiety in paediatric dental patients. Eur J Paediatr Dent. 2011 Dec;12(4):239-44. VCAS,2828 Venham L, Bengston D, Cipes M. Children's response to sequential dental visits. J Dent Res. 1977 May;56(5):454-9. https://doi.org/10.1177/00220345770560050101
https://doi.org/10.1177/0022034577056005...
and the FIS.2727 Buchanan H, Niven N. Validation of a Facial Image Scale to assess child dental anxiety. Int J Paediatr Dent. 2002 Jan;12(1):47-52.

Most studies showed that the subjective measure CFSS-DS did not correlate with salivary biomarkers.88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1515 Aoyagi-Naka K, Koda A, Kawakami T, Karibe H. Factors affecting psychological stress in children who cooperate with dental treatment: a pilot study. Eur J Paediatr Dent. 2013 Dec;14(4):263-8.,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
However, in one study, higher levels of salivary markers were observed in children whose parents/guardians had reported low dental fear, which may indicate that parent/guardians had limited knowledge of their children's feelings and emotions.1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
However, in another study, the levels of alpha amylase and salivary cortisol had a significant association with the level of dental fear, especially in patients who self-reported being phobic using the CFSS-DS.2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
Thus, the differences in correlation between objective and subjective measures in these studies might be explained by the use of parent/guardian or child responses.

Regarding parent's/guardian's reporting of children's dental anxiety, there was no positive or significant correlation between subjective measures and objective measures in most studies.1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
This finding sheds light on the assumption that parents tend to overestimate their children's anxiety.2929 Klein U, Manangkil R, DeWitt P. DeWitt. Parents’ ability to assess dental fear in their six- to 10-year-old children. Pediatr Dent. 2015 Sep-Oct;37(5):436-41. PMID:26531086 Other studies also found no significant correlation between dental anxiety score (DAS) and salivary cortisol level.3030 Sadi H, Finkelman M, Rosenberg M. Salivary cortisol, salivary alpha amylase, and the dental anxiety scale. Anesth Prog. 2013;60(2):46-53. https://doi.org/10.2344/0003-3006-60.2.46
https://doi.org/10.2344/0003-3006-60.2.4...
,3131 Brand HS. Anxiety and cortisol excretion correlate prior to dental treatment. Int Dent J. 1999 Dec;49(6):330-6. https://doi.org/10.1111/j.1875-595X.1999.tb00533.x
https://doi.org/10.1111/j.1875-595X.1999...
Krueger et al.3232 Krueger TH, Heller HW, Hauffa BP, Haake P, Exton MS, Schedlowski M. The dental anxiety scale and effects of dental fear on salivary cortisol. Percept Mot Skills. 2005 Feb;100(1):109-17. https://doi.org/10.2466/pms.100.1.109-117
https://doi.org/10.2466/pms.100.1.109-11...
found no correlation between dental anxiety and salivary cortisol in adult female individuals, although individuals were significantly more aroused and anxious prior to the treatment appointment. Only one study found a positive and significant correlation between anxiety reported by the children using the CDAS and cortisol levels as an objective measure prior to the procedure.1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
The children from this study were 13 years old, and although most of them were from a control group, some of the individuals in the sample were diagnosed with attention deficit hyperactivity disorder.1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
We can hypothesize that the methodological differences between the two types of measurements may be the reason for not finding a correlation in some of the cases. On the other hand, in those cases where a correlation does exist, the subjective measure may best reflect the child's state, besides being the easiest to collect in the dental setting.

In all included studies, invasive or/and noninvasive dental procedures were performed on children, which may have an influence on the interpretation of the results, since simple procedures, such as dental prophylaxis are less stressful99 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;16(1):74. https://doi.org/10.1186/s12903-016-0273-1
https://doi.org/10.1186/s12903-016-0273-...
than invasive procedures.3333 Miller CS, Dembo JB, Falace DA, Kaplan AL. Salivary cortisol response to dental treatment of varying stress. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):436-41. https://doi.org/10.1016/S1079-2104(05)80123-4
https://doi.org/10.1016/S1079-2104(05)80...
Also, procedures were performed under sedation in one study2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
and under general anesthesia in another study.1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
Thus, the different dental procedures, the non-standardization in the use of general anesthesia or sedation, and the use of different pharmacological techniques could represent a bias that prevents a clear determination of a correlation. This may have influenced the evaluation of the measures, since sedation and anesthesia are stressful procedures and may cause an endocrine change that increases salivary cortisol levels.3434 Hsu AA, von Elten K, Chan D, Flynn T, Walker K, Barnhill J, et al. Characterization of the cortisol stress response to sedation and anesthesia in children. J Clin Endocrinol Metab. 2012 Oct;97(10):E1830-5. https://doi.org/10.1210/jc.2012-1499
https://doi.org/10.1210/jc.2012-1499...
Moreover, sedation and anesthesia are prescribed for stressful operative procedures, so a significant increase in cortisol levels in these pediatric patients is not unexpected.3535 Taylor LK, Auchus RJ, Baskin LS, Miller WL. Cortisol response to operative stress with anesthesia in healthy children. J Clin Endocrinol Metab. 2013 Sep;98(9):3687-93. https://doi.org/10.1210/jc.2013-2148
https://doi.org/10.1210/jc.2013-2148...

Salivary cortisol was the most commonly used objective measure88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1616 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. https://doi.org/10.1111/j.1600-0722.2007.00423.x
https://doi.org/10.1111/j.1600-0722.2007...
,1818 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. https://doi.org/10.4103/0970-4388.155116
https://doi.org/10.4103/0970-4388.155116...
,2020 AlMaummar M, AlThabit HO, Pani S. The impact of dental treatment and age on salivary cortisol and alpha-amylase levels of patients with varying degrees of dental anxiety. BMC Oral Health. 2019 Sep;19(1):211. https://doi.org/10.1186/s12903-019-0901-7
https://doi.org/10.1186/s12903-019-0901-...
,2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
and seems to be the most appropriate biomarker for measuring stress and anxiety in the dental setting.3636 Nater UM, Rohleder N, Schlotz W, Ehlert U, Kirschbaum C. Determinants of the diurnal course of salivary alpha-amylase. Psychoneuroendocrinology. 2007 May;32(4):392-401. https://doi.org/10.1016/j.psyneuen.2007.02.007
https://doi.org/10.1016/j.psyneuen.2007....
3838 Kobayashi FY, Gavião MB, Marquezin MC, Fonseca FL, Montes AB, Barbosa TS, et al. Salivary stress biomarkers and anxiety symptoms in children with and without temporomandibular disorders. Braz Oral Res. 2017 Sep;31(0):e78. https://doi.org/10.1590/1807-3107bor-2017.vol31.0078
https://doi.org/10.1590/1807-3107bor-201...
Determination of cortisol in saliva is useful to assess children’ dental stress, not only because the result is reliable, but also because collecting a saliva sample is painless and less invasive and easier than collecting a blood sample. However, there are limitations due to circadian changes such as time of day and day of week. Also, the protein-binding capacity of the biomarker can vary and special devices are needed for sample collection and storage.3939 Lee DY, Kim E, Choi MH. Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB Rep. 2015 Apr;48(4):209-16. https://doi.org/10.5483/BMBRep.2015.48.4.275
https://doi.org/10.5483/BMBRep.2015.48.4...
This systematic review confirms that there is still a lack of agreement between self-reported of anxiety levels and biological stress reactivity4040 Hare OA, Wetherell MA, Smith MA. State anxiety and cortisol reactivity to skydiving in novice versus experienced skydivers. Physiol Behav. 2013 Jun;118:40-4. https://doi.org/10.1016/j.physbeh.2013.05.011
https://doi.org/10.1016/j.physbeh.2013.0...
or a lack of correlation between cortisol level and anxiety at certain periods of the day.4141 Simon DM, Corbett BA. Examining associations between anxiety and cortisol in high functioning male children with autism. J Neurodev Disord. 2013 Nov;5(1):32. https://doi.org/10.1186/1866-1955-5-32
https://doi.org/10.1186/1866-1955-5-32...

Although salivary chromogranin, an acid phosphorylated secretory glycoprotein, has been reported as a biomarker for the evaluation of acute stress episodes,4242 Fukui M, Hinode D, Yokoyama M, Yoshioka M, Kataoka K, Ito HO. Levels of salivary stress markers in patients with anxiety about halitosis. Arch Oral Biol. 2010 Nov;55(11):842-7. https://doi.org/10.1016/j.archoralbio.2010.07.014
https://doi.org/10.1016/j.archoralbio.20...
only two studies used it for the evaluation of dental anxiety in children,88 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. https://doi.org/10.3109/10253890.2014.918602
https://doi.org/10.3109/10253890.2014.91...
,1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
and the evidence for a relationship between salivary chromogranin A and dental anxiety has not been established yet.4343 Nakane H, Asami O, Yamada Y, Ohira H. Effect of negative air ions on computer operation, anxiety and salivary chromogranin A-like immunoreactivity. Int J Psychophysiol. 2002 Oct;46(1):85-9. https://doi.org/10.1016/S0167-8760(02)00067-3
https://doi.org/10.1016/S0167-8760(02)00...

This systematic review has limitations. First, although every effort was made to find all articles related to the topic, publication bias cannot be ruled out. Second, due to the heterogeneity of the included studies, a meta-analysis was not possible. However, we followed strict criteria to minimize error.1212 Higgins JP, Green S, eds. Cochrane handbook for systematic reviews of interventions version 5.1.0. S. l.: The Cochrane Collaboration; 2011.,1313 The Joanna Briggs Institute. Joanna Briggs Institute Reviewers’ Manual. Adelaide: The Joanna Briggs Institute; 2011. It should be noted that in some studies, questions about fear/anxiety were directed to parents/caregivers1717 Okano A, Miyamoto Y, Asari J, Kamijo R, Inoue M. Change in salivary levels of chromogranin A in children by hearing dental air turbine noise. Pediatr Dent J. 2009;19(2):220-7. https://doi.org/10.1016/S0917-2394(09)70177-6
https://doi.org/10.1016/S0917-2394(09)70...
,1919 Yıldırım S, Bakkal M, Bulut H, Selek S. Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia. Clin Oral Investig. 2018 Jul;22(6):2373-80. https://doi.org/10.1007/s00784-018-2340-2
https://doi.org/10.1007/s00784-018-2340-...
or the dentist.2121 Shanmugaavel AK, Asokan S, Baby JJ, Priya G, Gnana Devi J. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial. J Clin Pediatr Dent. 2016;40(1):81-7. https://doi.org/10.17796/1053-4628-40.1.81
https://doi.org/10.17796/1053-4628-40.1....
Although this assessment of perception cannot be considered a “patient-reported outcome”, in the context of pediatric research, proxy measures – PROMs – provide critical information about children. Another limitation was that we were unable to compare children's behavior with the other measures investigated because the included articles did not provide this information. This could be an important variable, as dental anxiety may predict children's behavior during dental treatment4444 Cohen LL, Francher A, MacLaren JE, Lim CS. Correlates of pediatric behavior and distress during intramuscular injections for invasive dental procedures. J Clin Pediatr Dent. 2006;31(1):44-7. https://doi.org/10.17796/jcpd.31.1.e803gj132m7226l6
https://doi.org/10.17796/jcpd.31.1.e803g...
and should be further assessed in future studies.

Conclusion

This systematic review found that the evidence of an association between objective salivary biomarkers and subjective patient-reported outcomes of dental fear or dental anxiety in the pediatric dental setting was of low/very low quality. Therefore, the information provided should be used cautiously. Studies of higher quality designed specifically to compare objective and subjective measures are needed.

Acknowledgements

We thank the Newton Fund 2016–2017 (British Council, UK), Fundação de Amparo à Pesquisa do Estado de Goias, Brazil, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the financial support to the workshop that enabled this working group.

We acknowledge the contribution of all CEDACORE (Children Experiencing Dental Anxiety: Collaboration on Research and Education) members in the discussions that underpinned this work.

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Publication Dates

  • Publication in this collection
    02 May 2022
  • Date of issue
    2022

History

  • Received
    18 Mar 2021
  • Reviewed
    02 Feb 2022
  • Accepted
    18 Feb 2022
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