1http://dx.doi.org/10.20396/bjos.v21i00.8666288 Volume 21 2022 e226288 Original Article 1 Department of Public Health Dentistry, Faculty of Dentistry, Universitas Jember, Jember, Indonesia. 2 Department of Biostatistics, Faculty of Public Health, Universitas Jember, Jember, Indonesia. 3 Department of Pediatric Dentistry, Faculty of Dentistry, Universitas Jember, Jember, Indonesia. Corresponding author: Elyda Akhya Afida Misrohmasari Faculty of Dentistry, Universitas Jember, Jl Kalimantan 37, Kampus Tegal Boto, Jember, Jawa Timur, Indonesia Tel/Fax: +62331 333536 E-mail: elyda.fkg@unej.ac.id Editor: Altair A. Del Bel Cury Received: July 6, 2021 Accepted: January 11, 2022 Toothache experiences: findings from 21 years longitudinal survey Elyda Akhya Afida Misrohmasari1,* , Dimas Wicaksono2 , Hestieyonini Hadnyanawati1 , Berlian Prihatiningrum3 Aim: To describe the pattern of toothache experience in a cohort of children aged 2-5 over 21 years and to find the relationship between previous toothache experience and later reports of toothache to get finding on the most critical period of toothache as a problem in life. Methods: This is a secondary data analysis from Indonesia Family Life Survey (IFLS). A total of 1,927 children from IFLS-1 with complete data were included as baseline participants. They were followed up four times within 21 years (age 6-9y, age 9-12y, age 16-19y, age 23- 26y). Toothache was based on the question of self-reported toothache experience during the last four weeks. After 21 years, a total of 1,098 individuals could be traced and completed every cohort of the survey. Toothache experiences were reported for frequencies in every cohort and accumulative experiences over 21 years. Logistic regression tests were performed to analyze the association of previous toothache experience and later toothache experience. Results: Almost 40% of the respondents reported toothache at least once in their life. The age of 6-9 years is the period when a high percentage of children had teeth-related pain. The experience of toothache at this period was significantly related to every period of age in life. Conclusions:  The period of early mixed dentition is important. Oral health status in this period is associated with future oral health. A comprehensive dental health prevention program targeting this population is essential to increase the quality of life. Keywords: Toothache. Longitudinal studies. Oral health. https://orcid.org/0000-0002-1791-113X https://orcid.org/0000-0002-8148-7433 https://orcid.org/0000-0002-8974-7201 https://orcid.org/0000-0002-0744-6123 2 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 Introduction A toothache is a public health problem because of its high prevalence and impacts among all age groups1-3. It is often mentioned as the most frequent type of orofacial pain4 and one of the major consequences of dental and oral health problems among children5,6. Toothache was also found to be experienced by 21.8% of adolescents7. More than one in ten people ≥65  years were also reported had a recent toothache experience. Moreover, toothache may have detrimental effects on individuals and society. Many studies showed that dental pain reduces sleep duration, increases school/work absences, and affects nutrition, which can negatively impact the quality of life8-10. Because of its significant effects on the life of people and society, the Global Goals for Oral Health in the year 2020 includes reduction of the episodes of oral pain in the population as one of the targets on oral health programs11. Information that toothache is the most mentioning problem in life is abundant, but understanding the importance of how the sequences is still questioning. Under- standing the sequences of toothache experience in a lifetime is crucial to prevent toothache in an appropriate period of life. The individual life-course approach to diseases is the critical period of development, which presumes that having expe- rience of certain conditions in early life can have long term impacts on later health outcomes12. We may understand that people in certain periods of life experience a higher rate of toothache in their life. However, there is limited study on tooth- ache using a life course approach. Most of the studies in dental pain are cross-sec- tional1,13-15. Few studies have focused on changes in toothache experiences at two or more points in time12,16-18. Some studies examined the trend of toothache over the different periods of life and found socioeconomic conditions were related to toothache experience. Previ- ous studies on toothache using longitudinal data in Brazil highlighted the relation of toothache to maternal education inequality remained stable from childhood and ado- lescence2. The prevalence of toothache among Brazilian adolescents increased and was found linked to race and region18. Another study in Brazil showed that the eco- nomically disadvantaged group had a higher prevalence of toothache in primary and mixed dentition17. Furthermore, a study in Australia found that lower-income family was related to more frequent toothache across the 14-years follow up12. Australian adults in the lowest socioeconomic group were found to have an increased preva- lence of toothache from 1994-201316. Considering the rare availability of recent studies on dental pain using a life course approach. This study aimed to address these problems by analyzing a 21 years lon- gitudinal study in Indonesia. The main advantage of this longitudinal study was the ability to estimate the trend in toothache over 21 years. Within this study period, chil- dren had primary dentition to permanent dentitions and became more independent and mature in adulthood. To our knowledge, there are no studies on toothache in which the same individuals have been followed up over a period as long as 21 years. Most studies examined dental pain using longitudinal data limited from childhood to adolescence4-6,18. In particular, this study bridging the understanding of toothache 3 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 experience in childhood, adolescence, and adulthood periods. Therefore, the aims were to describe the prevalance of toothache experience in a cohort of children aged 2-5 over 21 years to find the most critical period when toothache became the most serious problem and find the relationship between previous experience and later reports of toothache. Materials and methods Study design This study is a secondary data analysis from the Indonesia Family Life Survey (IFLS). The IFLS is an ongoing longitudinal household and community survey con- ducted by RAND Corporation in collaboration with many Indonesian institutions. The survey is a broad range survey that includes topics on health. The first survey started in 1993, with four subsequent rounds of data collection in 1997, 2000, 2007, and 2014. The survey dataset was obtained from the RAND Indonesia Family Life Survey website19. Setting and participants The first IFLS in 1993 covered a sample of around 7,200 households across 13 provinces in Indonesia20. This IFLS-1 encompassed approximately 83% of the Indo- nesian population. This survey collected data on individual household and commu- nity levels using multistage stratified sampling. This survey’s full details, includ- ing sampling methods and related protocols, can be found in the overview and field report20,21. The baseline data of this present study is the data of IFLS-1 in 1993 for 2-5 years old children as they were at the early stage of primary teeth. The flowchart for the sample collection carried out in this study can be seen in Figure 1. A total of 1,927 children from IFLS-1 with complete data on toothache experience and sociodemographic characteristics were included as baseline participants. This study excluded samples of missing data in all variable interests from statistical analysis. They were followed up four times within 21 years. The IFLS interviewer revisited the household in every follow-up period and conducted direct interviews with respondents from previous surveys. Target respondents who moved from the original residence will be tracked if only they moved in any one of the 13 IFLS provinces. The participants were at the age of 6-9 years when IFLS-2 was held in 1997 and 9-12 years old when IFLS-3 was held in 2000. The IFLS-4 was conducted in 2007 as the participants reached adolescence at 16-19 years old. The recent survey in 2014 was IFLS-5 when the participants were in early adulthood (age 23-26 years). In 2014, 1,098 individuals (57% of baseline participants) could be traced and com- pleted questionnaires on toothache and demographic characteristics in every fol- low up period. 4 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 Toothache Toothache as a variable interest in this study was assessed based on a question of toothache experience in the last four weeks with Yes-No answers. The interviews were conducted in Indonesian and the local language. At the 1st, 2nd, and 3rd fol- low-up, interviewers collected the data of toothache from parents or guardians, by the question “Has (child’s name) ever suffered from a toothache during the past 4 weeks?”. The toothache question can be found in the IFLS’s book 5, section MAA (acute morbidity), which asked questions on the health status and symptoms of chil- dren under 15 years old. At the 4th and 5th follow-up, toothache data was collected from a direct interview of the respondents by the question, “Did you ever experience a toothache in the last 4 weeks?”. For adults 15 years or older, the toothache question was presented in IFLS’s book 3B, section MA (acute morbidity) that asked questions about adult health symptoms. Sociodemographic characteristics In this study, sociodemographic characteristics of respondents were obtained from IFLS-1 data, which were included child sex, maternal education, number of persons in the house, and area of living. Sex was categorized into male and female. The maternal IFLS-1 in 1993 Age 2-5 y (n = 1927) IFLS-2 in 1997 Age 6-9 y (n = 1,786) IFLS-3 in 2000 Age 9-12 y (n = 1,740) IFLS 5 in 2014 Age 23-26 y (n = 1,098) IFLS-4 in 2007 Age 16-19 y (n = 1,434) Dropouts n = 141 (7.3%) Dropouts n = 46 (2.6%) Dropouts n = 306 (17.6%) Dropouts n = 336 (23.4%) Figure 1. IFLS flowchart in this study 5 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 education variable was simplified into three categories based on the highest educa- tion level attended by the participants’ mother from baseline data: primary or less, high school, and higher education level. In this study, the number of persons living in the house was categorized into three levels: 3 people or less, 4-5 people, and more than 5 people. The area of living categorization was urban and rural that were based upon 1993 SUSENAS (National Economic and Social Survey) listings obtained from regional BPS (Statistic Indonesia) office20. IFLS 1-5 conducted training for field coordinators, supervisors, interviewers, and edi- tors to establish inter-rater reliability21. The training was to ensure that people who gathered and entered the data in the field understood the same method for the details and technical knowledge of conducting the survey. This present study examined carefully how the data was collected and coded to minimize potential bias. Ethics This study is a secondary data analysis of a publicly available dataset. Procedures of the surveys were reviewed and approved by the Institutional Review Boards (IRBs) in the United States (at RAND) and in Indonesia at the University of Gadjah Mada (UGM). All respondents were given written informed consent before data collection. Data analysis Descriptive statistics of sociodemographic characteristics were retrieved from the participants at age 2-5 (IFLS-1). Toothache experiences were reported for frequencies in every cohort and accumulative experience over 21 years. Binary logistic regression tests were performed to analyze the association of previous toothache experiences and later toothache experiences. The level of significance was at p<0.05. The analysis was performed using SPSS 25. Results There were 1,927 children age 2-5 at baseline in 1993. In the follow-up periods, the number of participants decreased because they either died or moved to other prov- inces outside the survey areas. The participants were 1,786 in 1997, 1,740 in 2000, 1,434 in 2007, and 1,098 participants in 201completing all follow-ups. For every cohort, sociodemographic characteristics of participants were similar, except for sex. In 1993, the number of male participants was higher, but in 2014 more females (52.1%) were reinterviewed. More than 65% of the participants in this study had low education mothers. In this study, more than 50% of participants lived in rural areas with a family of 4-5 people. Detailed information on the sociodemographic characteristics of respondents can be found in Table 1. The toothache experience varied over time, which was reported among 155 children 2-5 years at baseline, 251 children in 1997, 208 children in 2000, 138 children in 2007, and 131 children in 2014 (Table 1). 6 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 Table 1. Distribution of sociodemographic characteristics and toothache experience among participants in every cohort (IFLS1-5) Variables IFLS-1 in 1993 (Age 2-5y) (N=1,927) IFLS-2 in 1997 (Age 6-9y) (N=1,786) IFLS-3 in 2000 (Age 9-12y) (N=1,740) IFLS-4 in 2007 (Age 16-19y (N=1,434) IFLS-5 in 2014 (Age 23-26y) (N=1,098) Sex Male 1,017 (52.8%) 935 (52.4%) 908 (52.2%) 736 (51.3%) 526 (47.9%) Female 910 (47.2%) 851 (47.6%) 832 (47.8%) 698 (48.7%) 572 (52.1%) Maternal education ≤ Primary 1,270 (65.9%) 1199 (67.1%) 1,174 (67.5%) 949 (66.2%) 745 (67.9%) High schools 547 (28.4%) 487 (27.3%) 469 (27.0%) 405 (28.2%) 288 (26.2%) Higher edu 110 ( 5.7%) 100 ( 5.6%) 97 (5.6%) 80 (5.6%) 65 (5.9%) Persons per household ≤ 3 324 (16.8%) 300 (16.8%) 288 (16.6%) 249 (17.4%) 197 (17.9%) 4-5 993 (51.5%) 993 (51.8%) 908 (52.2%) 744 (51.9%) 567 (51.6%) ≥ 6 610 (31.7%) 560 (31.4%) 544 (31.3%) 441 (30.8%) 334 (30.4%) Area Urban 854 (44.3%) 750 (42.0%) 725 (41.7%) 608 (42.4%) 440 (40.1%) Rural 1,073 (55.7%) 1,036 (58.0%) 1,015 (58.3%) 826 (57.6%) 658 (59.9%) Toothache Yes 155 (8.0%) 251(14.1%) 208 (12.0%) 136(9.5%) 131(11.9%) No 1,772 (92.0%) 1,535(85.9%) 1,532 (88.0%) 1,298(90.5%) 967(88.1%) Figure 2 illustrates the trend of toothache prevalence in a lifetime. In an early denti- tion period at age 2-5 years, toothache was reported by 8% of the population. When they reached the age of 6-9 years, 14% of children had teeth-related pain, which is the highest percentage over the surveys. At the age of 9-12 years, the proportion of participants who reported toothache decreased to 12%. Over the 21 years survey period, the prevalence of self-reported toothache was at the lowest level when they Figure 2. Toothache experiences in every period of life of the cohort participants 8% 14.10% 12% 9.50% 11.90% Age 2-5y Age 6-9y Age 9-12y Age 16-19y Age 23-26y Prevalence of Toothache Experince 7 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 reached the age of 16-19 years (9.5%). However, at the period of early adulthood at 23-26 years old, the percentage of participants reporting toothache was higher than the previous period at 11.9%. The 21 years accumulative reported toothache experience was presented in Table 2. Almost 40% of the respondents reported toothache at least once in their life. Table 2. Accumulative frequencies of toothache experiences over 21 years (N=1,098) N (%) None 662 (60.3%) Once 308 (28.1%) Twice 95 (8.7%) 3 times 27 (2.5%) 4 times 6 (0.5%) The result from binary logistic regression tests, as shown in Table 3, found that the age of 6-9 years consistently had a significant association with toothache experience in every model. Participants who experienced a toothache at age 6-9 were more likely to experience a toothache in every period of age later in life. Experience toothache at age 2-5 was more likely to experience a toothache at age 6-9 (p=0.036; OR=1.60). Tooth- ache experience at age 9-12 was significantly related only to toothache experience at age 6-9 (p <0.000; OR=2.20). At age 16-19, toothache experince was related to tooth- ache experience at age 6-9 (p<0.000; OR=2.53) and age 9-12 (p=0.001; OR=2.17). The experience of toothache at early adulthood (age 23-26 years) was significantly associated with toothache experience at the age of 6-9 years (p=0.042; OR=1.58) and 16-19 years (p<0.000; OR=2.86). Table 3. Regression model of the association between previous toothache experience and later toothache experience Toothache Model 1 Age 6-9y (N=1786) Model 2 Age 9-12y (N=1740) Model 3 Age 16-19y (N=1434) Model 4 Age 23-26y (N=1098) Sig OR 95% CI Sig OR 95% CI Sig OR 95% CI Sig OR 95%CI Age 2-5y 0.036 1.60 1.03-2.47 0.387 1.32 0.70-2.48 0.431 1.28 0.70-2.34 0.885 0.95 0.47-1.91 Age 6-9y <0.000 2.20 1.42-3.41 <0.000 2.53 1.68-3.81 0.042 1.58 1.02-2.45 Age 9-12y 0.001 2.17 1.39-3.40 0.924 0.97 0.56-1.70 Age 16-19y <0.000 2.86 1.72-4.76 p < 0.05; Binary Logistic Regression OR=odds ratio; CI=confidence interval Discussion This longitudinal study followed a group of children age 2-5 years in IFLS 1993 over 21 years. The aims were to find the prevalence of toothache in every age period and seek the association between previous toothache experience and later life. The 8 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 toothache experience was based on the self-reported toothache during the last four weeks. This study found that the highest percentage of toothache was reported at age 6-9 years. The toothache experience in this period was also related to the tooth- ache experience in subsequent periods of life. The prevalence of toothache at the age of 2-5 years is 8%, the lowest compared to the later periods of life. This result is lower than the prevalence of toothache in pre- school children in Brazil at age 3-4 years with 11.8%22 and of preschool children age 2-4 years in Australia (15%)23. All primary teeth erupt into the mouth by two years of age. Children learn to brush their teeth under supervision in this period of age24. Most of the toothache in children found related to caries6. Caries development into a symp- tom needs a period of time5. Therefore, most children reported no toothache due to the early tooth wear in this age group. It is essential that children’s oral health was assessed from a very young age, and oral health behavior was formulated to prevent negative impacts on later life. When children reached the age of 6-9 years in 1997, the toothache was reported by 14.1% of the participants in this study. This prevalence is the highest over 21 years of study. The toothache experience in this age period is significantly associated with every period of age in later life, from adolescence to early adulthood. Age of 6–7 years, children go through a critical transition phase of both psychological and biological development25. General anxiety, physical injury, and fears such as separation from parents are present during this period of life25. This age period is also an early transi- tional period of the mixed dentition, with exfoliation of primary teeth and eruption of permanent teeth. Tooth mobility in this transition phase can be a factor in reporting toothache25. This age is also the period when children become more independent and develop more mature motoric skills5. The prevalence of toothache in 6-9 years children in this study is similar to a study in the United States (14%)26 and slightly lower than toothache experience of children age seven years in Sweden with about 15%27. This prevalence is lower than 49.9% reported from 6-12 years old school children in Mexico14. However, a study in Canada reported a lower percentage of toothache at around 5% of children28. The difference in toothache prevalence can be related to many factors, including the development context of different locations and countries, variations of the disease level between populations, health system management and actions on population oral health prob- lems, and also methodologies applied in every study. This study found that in the late phase of mixed dentition, children age 9-12, reported less frequent toothache experience than the previous age period (12%). This result was lower than a study in South Brazil for children 8-12 years that reported tooth- ache experience for 17.3% of the population29 and a study for children age 9-12 years in Australia (27.4%)12. This number is also lower than a study in Taiwan where more than 30% of children experience dental pain during the past year15. In this period of life, children begin to have the ability to judge their behavior and emotion, including the awareness of their physical appearance and other’s thought30. In the adolescent period (age 16-19 years), 9.5% of the participants in this study reported toothache experience in the last four weeks. This result is slightly lower 9 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 than around 10% of Canadian adolescents who reported toothache28. A study of ado- lescence age 15-19 in Brazil found that 28.3% of participants experience toothache during the last six months31. Adolescence is an intermediate period between child- hood and adulthood, characterized by intense psychological and physical changes32. In this transitional phase, individuals may involve in particular behaviors that can compromise their health status4. The experience of toothache in this period is signifi- cantly related to the toothache experience in childhood. Self-reported toothache at the age of 23-26 years was 11.9%. This number is lower than a study in Brazil among 20-29 years adult (17.2%)33 and a young adult popu- lation in Canada 14%28. The experience of toothache in this period was significantly associated with toothache experience at early mixed dentition and adolescence. A similar result was also found in which followed individuals from late childhood into early adulthood. The DMFT and CPI values at age 18 years were associated with DMFT and CPITN scores at younger ages34. Over 21 years of study, almost 40% of the respondents had ever experienced a toothache. This study reported that having toothache experience in early life was an important determinant for future toothache experience in this life course study5. The high prev- alence of toothache in the early mixed dentition period and its significant association with future toothache experiences suggest the need to create comprehensive dental health prevention programs targeting this population to reduce the impact of pain on their quality of life. The strengths of this study were the participants’ follow-up over 21 years and the high number of participants involved. This study could be a reason to describe the trend in toothache experience over time. A longitudinal study design had a reliable estimate of the change in toothache experience over the 21 years of the study. The life course models are useful to understand the long-term effects of exposures during childhood, adolescence, young adulthood, and later adult life on chronic disease35. Some limitations are found in this study. First is the loss of follow-up at the survey. A considerable number of participants in this study cohort were lost at the IFLS-4 and IFLS-5 when they reached adolescence and adulthood. Second, due to secondary data analysis of this study, data available limited in terms of information related to oral health, limiting the authors to draw a more comprehensive analysis. Future stud- ies may consider more comprehensive variables, including socioeconomic factors and other oral health behaviors, such as dietary habits, tooth brushing frequency, to explore the mechanisms of the statistical association found in this study. Data availability Datasets related to this article can be found at  https://www.rand.org/well-being/ social-and-behavioral-policy/data/FLS/IFLS/access.html. Authors’ contribution Elyda Misrohmasari: Design, Interpretation, Drafting, Revising Dimas Wicaksono: Acquisition, Analisis, Revising 10 Misrohmasari et al. Braz J Oral Sci. 2022;21:e226288 Hestieyonini Hadnyanawati: Design, Interpretation, Revising Berlian Prihatiningrum: Interpretation, Revising All of the authors listed have been read and approved to submit the manuscript to this journal. All authors agree to be accountable for all aspects of the work. References 1. Muirhead VE, Quayyum Z, Markey D, Weston-Price S, Kimber A, Rouse W, et al. 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