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. 2024 Dec 6;19(12):e0313024. doi: 10.1371/journal.pone.0313024

Bruxism associated with short sleep duration in children with autism spectrum disorder: The Japan Environment and Children’s Study

Masahiro Tsuchiya 1,*, Shinobu Tsuchiya 2,3, Haruki Momma 4, Ryoichi Nagatomi 4,5, Nobuo Yaegashi 6,7, Takahiro Arima 8, Chiharu Ota 7, Kaoru Igarashi 2,3; the Japan Environment and Children’s Study Group
Editor: Ayako Mochizuki9
PMCID: PMC11623795  PMID: 39642159

Abstract

Bruxism, the involuntary activity of masticatory muscles, is common among individuals with autism spectrum disorders (ASD). Although bruxism is bidirectionally associated with sleep issues, whether an infant’s sleep duration contributes to the development of bruxism remains unknown. In this study, a dataset (n = 83,720) obtained from the Japan Environment and Children’s Study, a nationwide birth cohort study, was subjected to multiple imputations using logistic regression analysis with adjustments for several maternal and child-related variables. The aim of this study was to assess whether shorter sleep duration in the neonatal period additively affected the high prevalence of parent-reported bruxism (PRB) among children with ASD. The prevalences of ASD and PRB in the participants were 1.2% and 7.2%, respectively, and the odds ratio of the increased risk of PRB prevalence in individuals with ASD (95% confidence interval) was 1.59 (1.31–1.94) after covariate adjustments. Importantly, shorter sleep duration in the neonatal period (at one month of age) was significantly associated with an increased risk of PRB prevalence in individuals with ASD. The increased occurrence of bruxism, known to be highly prevalent among children with ASD, is associated with shorter sleep duration, particularly in the neonatal stage. Based on our results, a better understanding of the development of bruxism in individuals with ASD would provide valuable information for the prevention of oral diseases.

Introduction

Bruxism is an involuntary and repetitive oral parafunctional activity, which includes teeth clenching, grinding, bracing, and/or thrusting, specified as either sleep or awake bruxism [1, 2]. Bruxism appears with tooth eruption, tends to be habitual with growth [3], and is reportedly more prevalent in children than in adults (14–20% in children, 8% in adults <60 years old, and 3% in adults >60 years old) [4]. Habitual and/or excessive bruxism potentially aggravates orofacial tissue damage, such as tooth wear or temporomandibular disorders [5, 6]. Bruxism has multiple causal factors comprising pathophysiological and psychosocial issues [79]. Development of bruxism related to other underlying diseases, including neurodevelopmental disorders such as autism spectrum disorder (ASD) and cerebral palsy, is considered secondary bruxism [8]. A systematic review showed that bruxism is approximately four times more prevalent among individuals with ASD than in those with typical development [10]. In particular, since some medications for ASD potentially aggravate bruxism [7, 11], the risk of developing oral health issues such as tooth wear and orofacial pain is high in individuals with ASD [12, 13]. Thus, further research is required to understand the occurrence of bruxism in children with ASD for properly managing oral health problems.

ASD is a constellation of neurodevelopmental disorders with multiple delays and behavioral deviations that manifest during early childhood, predominantly in males, with a worldwide prevalence of approximately 1 in 100 children [14, 15]. As early diagnosis of ASD and proper intervention involving both the affected children and their parents is essential, recent advances in multidisciplinary interventional approaches in early childhood have contributed substantially to the improvement of physiological and psychosocial development [16, 17]. As bruxism’s etiology [10, 18], individuals with ASD show a higher prevalence of sleep problems, with divergent patterns that emerge in early childhood [19, 20]. Appropriate sleep behaviors in early childhood contribute to healthy physical and mental development in children [21, 22]. Studies have shown a bidirectional etiological association between bruxism prevalence and sleep issues [1, 23, 24]. Our latest work using a dataset from a nationwide prospective birth cohort study also showed that shorter sleep duration in the neonatal stage additively increased the occurrence of bruxism in children [24]. Thus, sleep issues in early childhood potentially exacerbate the high prevalence of bruxism among individuals with ASD; however, information regarding the association between sleep disorders in infants who later develop ASD and the occurrence of bruxism in early childhood is lacking.

Herein, using a dataset from the Japan Environment and Children’s Study (JECS), an ongoing nationwide, multicenter, prospective birth cohort study [24], we examined whether shorter sleep duration in early childhood prospectively impacts the prevalence of parent-reported bruxism (PRB) in children with ASD more than that in typically developing children.

Methods

This cross-sectional study followed the “STROBE” guideline for cross-sectional studies [25] (S1 Text).

Study design and participants

The JECS was conducted in accordance with the Declaration of Helsinki (announced in 1975 and revised in 2008), and the protocol was reviewed and approved by the Institutional Review Board on Epidemiological Studies of the Ministry of Environment and the Ethics Committees of all participating institutions (no. 100910001 and no. 2023–017), as described previously [26, 27]. The aim and procedure of the study were explained to all participants, and written informed consent was obtained before their participation. This study was conducted as a part of the JECS and anonymized data were used. Recruitments of the JECS started from January 2011 to March 2014. This study was based on the jecs-ta-20190930-qsn and jecs-qa-20210401 datasets, which were released in October 2019 and April 2021, respectively.

Pregnant women were recruited in the JECS during their first prenatal examination by cooperating healthcare providers in local government offices between January 2011 and March 2014. After the participating mothers completed a self-administered questionnaire, medical doctors and trained nurses performed clinical measurements and summarized the medical record transcripts. Of the 104,059 pregnancies from 15 Regional Centres included in the JECS, 3,759 resulted in miscarriages, stillbirths, or loss of follow-up. Furthermore, 16,580 participating mothers did not respond to the questionnaires, which asked about ASD diagnosis at the ages of 3 and 4 years or prevalence of PRB at the ages of 2 and 4 years. After excluding these participants from the analysis, the final sample included 83,720 children (Fig 1).

Fig 1. Flow chart of the study participants.

Fig 1

Occurrence of bruxism (outcome measure)

Prevalence of PRB was assessed in children aged between 2 and 4 years using a questionnaire reported by the caregivers, which included Yes/No questions, such as “Does your child have bruxism?” [24, 28].v PRB included all types of bruxism such as grinding and clenching, observed as either sleep or awake bruxism. As consistent prevalence of PRB would improve the reproducibility of the results obtained using parent-administered questionnaires, participants with bruxism reported by caregivers at both time points (2 and 4 years of age) were placed in the PRB group and analyzed further. Thus, prevalence of PRB was considered a binary variable defined by its absence or presence.

Prevalence of ASD (main exposure measure)

The prevalence of ASD in participants was determined using questionnaires mailed 3 and 4 years after delivery. Parents or caregivers of the participants were asked the following question: “Has your child ever been diagnosed with the following diseases and/or disorders by a doctor?” In the section on various childhood diseases and/or disorders, there was a checkbox for “ASD”. The participant was considered to have ASD if the ASD checkbox was marked at each age point. In our cross-sectional design, the prevalence of ASD was recorded as a binary variable, being either absent or present.

Sleep duration in early childhood (secondary exposure measure)

The daily sleep duration of the participants in early childhood was estimated at 1, 6, 12, 18, and 36 months after delivery, using a follow-up questionnaire. Parents or caregivers marked the questionnaire by drawing lines through checkboxes indicating 30-min intervals from 12:00 am on each day to 12:00 am on the next day [24, 29]. Sleep duration was considered a continuous and categorical variable in the analysis. For categorizing sleep duration at each time point, the participants were categorized into four 2-h groups (e.g., each 2-h group ranges from equal to or below 13 h to more than 17 h at 1 month of age) by arranging the median in the central group at each time point. Furthermore, participants were categorized into two groups (≤13 h and >13 h), which were used as the binary variable to estimate the interaction between short sleep duration at 1 month of age and ASD prevalence.

Covariates

The detailed design of the questionnaire has been described previously [24, 26, 30]. Briefly, sociodemographic characteristics, lifestyle, and health status in mother-infant dyads, which have been previously reported as confounding variables [1, 31], were included as covariates in the analysis models. Information, such as annual household income, maternal educational level, smoking habits, and drink intake, was assessed using a self-administered questionnaire filled by the mothers during pregnancy. Maternal age at delivery and child sex were retrieved from the medical record transcripts. The presence of siblings was also assessed using a follow-up questionnaire at 4 years postpartum. All data were retrieved using medical record transcripts and self-administered questionnaires. Additionally, the prevalence of congenital anomalies was ascertained in 8,764 (8.5%) infants from medical record transcripts and questionnaires. Details regarding data processing, validation, and verification of congenital anomalies have been described previously [27, 32].

Using the data, the participants were categorized into different groups based on the following variables: annual household income in Japanese yen (<2 million, 2−4 million, 4−6 million, or ≥6 million); maternal educational level (junior or high school, junior college [technical or junior college], or university [university or graduate]); maternal smoking history (never smoked, stopped smoking before or during pregnancy [previously did but quit before realizing current pregnancy; previously did but quit after realizing current pregnancy], currently smoking); alcohol intake (never consumed, stopped drinking, or current drinker); sex of the child (male or female); siblings of the child (presence or absence); and the prevalence of congenital disease (presence or absence).

Statistical analysis

Of the 83,720 participants, data on ASD diagnosis at 3 and 4 years of age were missing for 2,380 (2.8%) and 5,589 children (6.7%), respectively. Data on PRB was missing for 2,378 (2.8%) and 5,717 (6.8%) participants at 2 and 4 years of age, respectively. Multiple imputations using the multivariate normal imputation method with the “missing at random” assumption were applied to the missing data [33]. An imputation model that included all variables (including the main exposure and outcome variables) used in the main analysis was independently applied to 10 copies of the data, each of which contained suitably imputed missing values. According to Rubin’s rules, the imputed values of the variables should be estimated using the means and adjusted standard errors obtained from the observed data [34].

The baseline characteristics of the patients are summarized in Table 1. Maternal age at delivery and the child’s sleep duration are presented as median with interquartile range and mean with standard deviation (SD), respectively. Categorical variables were presented as numbers and percentiles. All statistical analyses were conducted using the IBM SPSS Statistics software (version 24.0; IBM Corp., Armonk, NY, USA), and p-values less than 0.05 were considered significant.

Table 1. Baseline characteristics of children (n = 83,720) participating in the JECS (2011−2015).

Control ASD
Child’s PRB Absence, n (%) Presence, n (%) Absence, n (%) Presence, n (%)
76,823 (92.9) 5,884 (7.1) 887 (87.6) 126 (12.4)
Age at delivery, median (IQR)
31 (28, 35) 31 (27, 35) 32 (28, 36) 32 (29, 35)
Infant’s sleep duration at months after delivery; mean (SD) in hours
1 14.9 (3.4) 14.5 (3.5) 14.4 (3.7) 13.3 (4.6)
6 13.6 (2.2) 13.4 (2.3) 13.4 (2.3) 13.5 (1.6)
12 12.8 (1.9) 12.8 (2.0) 12.8 (1.9) 12.8 (1.8)
18 12.3 (1.8) 12.2 (2.0) 12.2 (2.0) 12.2 (1.8)
36 11.5 (1.6) 11.5 (1.6) 11.4 (1.6) 11.4 (1.1)
Child’s sex
Male 38,743 (92.0) 3,370 (8.0) 673 (87.0) 100 (13.0)
Female 38,080 (93.8) 2,514 (6.2) 214 (89.3) 26 (10.7)
Sibling(s)
Absence 18,543 (89.1) 2,266 (10.9) 296 (83.4) 59 (16.6)
Presence 58,280 (94.2) 3,618 (5.8) 591 (89.8) 67 (10.2)
Household income (million yen/ year)
<2 3,917 (91.6) 358 (8.4) 51 (93.4) 4 (6.6)
2 to <4 26,124 (92.5) 2,127 (7.5) 320 (85.7) 53 (14.3)
4 to <6 25,694 (93.1) 1,896 (6.9) 304 (87.1) 45 (12.9)
≥6 21,088 (93.3) 1,503 (6.7) 212 (89.7) 24 (10.3)
Educational attainment
High school or less 25,985 (92.4) 2,146 (7.6) 319 (88.1) 43 (11.9)
Junior college 33,068 (93.0) 2,492 (7.0) 353 (86.9) 53 (13.1)
University or higher 17,770 (93.4) 1,246 (6.6) 215 (87.7) 30 (12.3)
Smoking habit
Never 46,530 (93.3) 3,360 (6.7) 516 (87.5) 74 (12.5)
Stopped 27,424 (92.5) 2,220 (7.5) 331 (88.9) 41 (11.1)
Smoking 2,869 (90.4) 304 (9.6) 40 (78.2) 11 (21.8)
Alcohol intake
Never 26,900 (93.4) 1,911 (6.6) 293 (85.3) 51 (14.7)
Stopped 42,141 (92.6) 3,380 (7.4) 520 (87.8) 72 (12.2)
Drinking 7,782 (92.9) 593 (7.1) 74 (95.9) 3 (4.1)
Congenital diseases
Absence 69,913 (93.0) 5,224 (7.0) 753 (87.8) 105 (12.2)
Presence 6,910 (91.3) 660 (8.7) 134 (86.4) 21 (13.6)

ASD = autism spectrum disorders; IQR = interquartile range; PRB = parent-reported bruxism; SD = standard deviation.

For analyzing the association of PRB prevalence with that of ASD in children, binomial logistic regression analysis involving the potential covariates obtained using the simultaneous method was performed and the odds ratios (ORs) for PRB were estimated; the control group was used as the reference. For crude or adjusted analyses using the aforementioned covariates, Model 1 was analyzed after adjusting for maternal age at delivery and sex of the child. The variables included in Models 1 and 2 included maternal factors (educational attainment, smoking, and drinking habits), infant factors (presence of siblings and prevalence of congenital diseases), and household income. Additionally, Model 3 included the infants’ sleep duration at 1 month of age as a continuous variable (Table 2). ORs and 95% confidence intervals (95% CIs) were calculated for PRB. After stratification by the prevalence of ASD, patient subgroup analysis of the association between PRB and infant sleep duration, which was used both as the continuous and ordinal variable, was performed. When used as an ordinal variable, the group with the shortest sleep duration was designated the reference group.

Table 2. Association between prevalence of PRB and ASD.

Control ASD
Presence, n (%) 5,884 (7.1) 126 (12.4) p-value
Crude Ref 1.86 (1.53–2.26) <0.001
Model 1a 1.76 (1.45–2.15) <0.001
Model 2b 1.61 (1.32–1.96) <0.001
Model 3c 1.59 (1.31–1.94) <0.001

ASD = autism spectrum disorders; PRB = parent-reported bruxism.

Odds ratio (95% confidence interval) (all such values).

aAdjusted for maternal age and infant’s sex.

bAdditionally adjusted for maternal factors (educational attainment, smoking, and drinking habits), household income, and presence of sibling(s) in infants in Model 1.

cAdditionally adjusted for the infant’s sleep duration at 1 month of age in Model 2.

Results

The baseline characteristics of the participants according to the prevalence of ASD and PRB (at both 2 and 4 years after delivery) are presented in Table 1. ASD was estimated to be prevalent in 1,014 children (1.2%). Of these, 383 participants (0.5%) were diagnosed 3 years after delivery. Additionally, 13,924 (16.6%) and 19,022 (22.7%) participants presented with bruxism, as reported by caregivers, at 2 and 4 years of age, respectively. PRB was observed in 5,884 (7.1%) and 126 (12.4%) participants in the control and ASD groups, respectively. Notably, 3,470 (8.1%) and 2,540 (6.2%) were males and females with PRB, respectively. Furthermore, the mean sleep duration of participants with PRB was significantly shorter than that of the controls, particularly at 1 month, but not at other months after delivery. As shown in S1 Table, the highest occurrence of PRB was found in the group with the shortest sleep duration among all participants until 6 months after delivery, but not at later time points.

The crude and adjusted ORs of ASD for PRB were calculated using multivariate logistic regression analysis (Table 2). The OR (95% CI) for prevalence of PRB in the adjusted model for all covariates increased with the prevalence of ASD (1.59 [1.31–1.94]). Notably, in an adjusted model for all covariates, the OR (95% CI) for the prevalence of PRB was 0.98 (0.97–0.99) for per hour increase in sleep duration in children aged 1 month.

Next, we focused on the association between children’s sleep duration in early childhood and the prevalence of PRB in participants with ASD, stratified by participants with prevalence. The participants’ baseline association of sleep duration at each time point with the prevalence of ASD and PRB is presented in S1 Table. In participants of the shortest sleep duration group (used as the reference), the crude and adjusted ORs for the prevalence of PRB decreased consistently with longer sleep duration at 1 month of age regardless of the prevalence of ASD (S2 Table). The ORs (95% CIs) for the prevalence of PRB for per hour increase in sleep duration in the control and ASD groups were 0.98 (0.97–0.99) and 0.95 (0.90–0.99), respectively. However, the lower ORs of longer sleep duration for the prevalence of PRB were not observed after 6 months in participants with ASD (S2 Table).

Furthermore, we analyzed the interaction between ASD prevalence and short sleep duration at 1 month of age (≤13) with the prevalence of PRB. Compared with that in the reference group (participants having normal sleep duration [>13 h] in the control group), short sleep duration (1.17 [1.10–1.25], p < 0.001) and prevalence of ASD (1.38 [1.08–1.78], p = 0.012) were associated with increased ORs (95% CIs) for the prevalence of PRB in the adjusted model for all covariates. The OR (95% CIs) for the prevalence of PRB in ASD participants having short sleep duration was 2.46 (1.80–3.38, p < 0.001) (Fig 2). Notably, a significant interaction between ASD and short sleep duration was observed (1.52 [1.02–2.23], p < 0.05).

Fig 2. Interactive impact of ASD prevalence and short sleep duration on the occurrence of PRB at 1 month of age.

Fig 2

Discussion

In this study, we analyzed the data obtained from a large-scale nationwide birth cohort in Japan. The key findings were that shorter sleep duration in the neonatal period was additively associated with developing PRB in children with ASD, with an approximately 1.6-fold higher risk of PRB prevalence, than children with typical development. As poor oral health is common among people with ASD, a better understanding of the relationship between bruxism prevalence and sleep issues would help in maintaining the oral health of such individuals.

Shorter sleep duration in the neonatal period remarkably impacts the occurrence of PRB in children regardless of the prevalence of ASD, although the association was more significant in children with ASD. The frequency of sleep disturbances in individuals with both ASD and PRB prevalence has been reported previously [10, 18, 23, 35]. In particular, sleep-onset problems associated with ASD are common in infants [19]. However, studies investigating the mechanism underlying the etiopathology of predominant bruxism in individuals with ASD and its involvement with sleep issues are limited [10, 36]. The mean difference in sleep duration between children aged 1 month with and without prevalence of PRB was higher in those with ASD (1.1 h vs. 0.4 h in the control group). Comparison of the effects between participants with and without ASD showed that the short sleep duration at 1 month of age (≤13 h) was dominantly associated with high prevalence of PRB in children with ASD (Fig 2). Sleep issues increase the risk of bruxism prevalence; however, the evidence provided is insufficient [10, 18]. Brainstem function develops remarkably in newborns and contributes significantly to sleep development in infants [37], as well as to ASD aggravation [38]. Previous studies have outlined the primary targets that potentially induce involuntary bruxism [1, 39]. However, further studies focusing on brain development and behavioral sleep interventions in early childhood are warranted to determine the mechanisms underlying the behavioral development of excessive bruxism in children with ASD, specifically regarding sleep issues during the neonatal period.

A systematic review of case-controlled trials [10] revealed that the prevalence of PRB was consistently high in children with ASD. However, the increased risk in our study (approximately 1.6-fold) was relatively lower than that in a previous systematic review (approximately 4-fold of the control) [10]. In addition to the difference in study designs between case-control and cohort studies, the participants in whom the onset of bruxism in early childhood was investigated were younger than those included in previous studies owing to the design of the birth cohort study. Treatment with ASD medications is generally started at around the preschool age, some of which potentially aggravate bruxism [7, 11]. Additionally, one-third to half of ASD cases were reportedly identified after 6 years in participants with undiagnosed ASD [40]. The proportion of children with ASD in this study was not low [15], although potential patients with ASD were included in the control group. Therefore, the risk of bruxism is expected to be high in mature participants; however, further investigations are required.

A child’s sex can directly impact both early-stage neurodevelopment and the prevalence of ASD [14, 15]. Concerning the impact of sex differences on the results, the prevalence of PRB in male participants was higher than that in females (8.1% vs. 6.2% in females), and the OR (95% CI) in males was 1.32 (1.25–1.39, p < 0.001) in the adjusted model for all variables, including the prevalence of ASD, a male-dominant disorder. Despite the controversy regarding the sex-based differences in the prevalence of bruxism owing to the different diagnostic criteria and study designs used in previous studies, the prevalence of bruxism in males, as shown in this study, is consistent with that reported by others [41, 42]. In conclusion, regardless of sex-specific differences, excessive bruxism observed in patients with ASD increases the risk of various oral health problems, including periodontal diseases, malocclusion, and tooth wear [18, 4345]. Thus, based on the observations regarding the deteriorated oral development and hygiene [12, 13]. our findings can provide valuable information for preventing negative health events in children with ASD.

Our study has several advantages and limitations. The JECS dataset used in our study was obtained from a nationwide Japanese survey that included almost half of all the infants born in several regions from 2011 to 2014 [24, 26, 30]. Thus, the findings, mostly based on the common Japanese population, allowed us to compare the behavioral onset of PRB in children with ASD and its association with the infants’ sleep duration with abundant control participants. However, owing to the collection methods used, limitations associated with this dataset exist, particularly those regarding insufficient information on the type and frequency of bruxism. Since the questionnaire did not include a query regarding the diagnostic validity and classification of bruxism, the PRB included all types and severities of bruxism (e.g., grinding and clenching during sleeping and wakefulness) in this study. In addition, Ishimaru and his colleagues have recently suggested a lower concordance between self-reported and device-detected bruxism (during both sleeping and waking) at an interindividual level [46, 47]. Although unfavorable in early childhood, direct measurements, such as those obtained using electromyography for estimating sleep bruxism, can provide more accurate data during sleeping and waking.

Conclusion

In conclusion, shorter sleep duration in the neonatal period potentially contributes to an increased risk of developing bruxism in children with ASD. Further studies with accurate estimation of bruxism in children with ASD are warranted.

Supporting information

S1 Text. STROBE statement.

(DOCX)

pone.0313024.s001.docx (36KB, docx)
S1 Table. Baseline association of sleep duration with the prevalence of PRB in 83,720 children.

(DOCX)

pone.0313024.s002.docx (38.6KB, docx)
S2 Table. Association of sleep duration with the prevalence of PRB in infants with or without ASD.

(DOCX)

pone.0313024.s003.docx (52.9KB, docx)

Acknowledgments

We thank all the JECS participants and the JECS staff members for conducting the procedure and helping with the data analysis.

Members of the JECS Group as of 2023: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan, kamijima@med.nagoya-cu.ac.jp), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Tomotaka Sobue (Osaka University, Suita, Japan), Masayuki Shima (Hyogo Medical University, Nishinomiya, Japan), Seiji Kageyama (Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Shoichi Ohga (Kyushu University, Fukuoka, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan).

The findings and conclusions of this article are solely the responsibility of the authors and do not represent the official views of the Japanese government. We also thank Editage (www.editage.com) for English language editing.

Data Availability

Data are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Medical and Health Research Involving Human Subjects enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restricts the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.

Funding Statement

The Japan Environment and Children’s Study was funded by the Ministry of the Environment, Government of Japan. The funding source had no role in the study design, analysis and interpretation of data, the writing of the report, and in the decision to submit the article for publication.

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Decision Letter 0

Ayako Mochizuki

5 Jun 2024

PONE-D-24-13310Behavioral occurrence of bruxism in children with autism spectrum disorder:the Japan Environment and Children's Study (JECS)PLOS ONE

Dear Dr. Tsuchiya,

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Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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5. Review Comments to the Author

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Reviewer #1: In this study, a dataset (n = 83,720) obtained from the Japan Environment and Children's Study (JECS), a nationwide birth cohort study was subjected to multiple imputation for verifying an increased prevalence rate of bruxism behavior in children with ASD. Additionally, the association between habitual bruxism in participants with ASD and sleep duration in infants on bruxism was examined using logistic regression analysis with adjustments for several maternal and child-related variables. The prevalence of ASD and habitual bruxism was 1.2% and 7.2%,

respectively. The odds ratio of the increased risk of bruxism in individuals with ASD (95% confidence interval) was 1.59 (1.31–1.94) after covariate adjustments. Furthermore, a longer sleep duration in the neonatal period was significantly associated with a decreased risk of habitual bruxism in participants with ASD. The results of this study

show that habitual bruxism is highly prevalent among children with ASD and is associated with sleep duration, particularly in the neonatal stage. The results of this study are interesting, and this article is well written. However, the following minor concerns should be addressed.

1) Emerging evidences suggest that dysbiosis of gut microbiota plays a role in ASD, and that oral microbiota may in part be regulated by gut microbiota. Please discuss a potential role of dysbiosis in oral microbiota and subsequent poor oral care in bruxism of ASD children.

2) Table 1: Prevalence of ASD in boy is higher than that of girl. is there a significant gender difference in bruxism in this study?

Overall, this study was conducted well, and this article is interesting.

Reviewer #2: [General comments]

This study attempted to examine the increased prevalence of bruxism in children with ASD, and the relationship between the prevalence of bruxism and sleep duration in infants. The objective of the study was vague, the expression of novelty in the introduction and discussion is unclear, and the differences with the results of the previous papers are unclear. Furthermore, the definition of bruxism was not explained sufficiently. Bruxism was assessed solely through a questionnaire, but the diagnostic validity of this is questionable.

Without sufficient explanation and improvements on these critical points, it is difficult to recommend this paper for publication in PLOS ONE.

[Detailed concerns]

Introduction

#1

The authors should clarify what had not been clarified in the previous researches and mention specifically which part of the characteristics of the relation between bruxism and ASD was tried to clarify in this research. More clear statement on objectives is needed. It is probably better method to present a specific hypothesis.

#2

Is the bruxism in ASD patients classified as secondary bruxism (symptomatic bruxism)?

It should be stated how the previous studies dealt with and how the authors had recognized for conducting this study.

#3

In the introduction part, some comments on drug-induced factors on ASD and bruxism should also be described.

#4 It should also be made clear whether the bruxism objected in this study is sleep bruxism and/or awake bruxism.

Methods

#5

A clear definition of "bruxism" should be presented. Further, the definition of "habitual bruxism" should be made clear in terms of definitions in previous studies, definitions at international conferences etc. In addition, the local definition of "bruxism" within this paper and the reason for adopt the definition should also be stated.

#6

It is necessary to provide a detailed explanation of the method for assessing bruxism. The contents of the reference studies should also be explained. The validity of diagnosing by interview alone should be discussed in the method part and/or the discussion part. This might had better be added as a limitation in the discussion part.

Results

#7

The following items should be written in more understandable manner: 1. The relationship between sleep duration and the prevalence of bruxism, 2. The relationship between ASD and the prevalence of bruxism, and 3. Whether the influence of sleep duration is greater in ASD patients than in controls.

#8

P15L218

It is questionable whether the following sentences can explain the characteristic that bruxism of individuals with ASD are more susceptible to the influences of sleep duration than controls.

“The ORs (95%CIs) for habitual bruxism per hour increase of sleep duration in the control and ASD groups were 0.98 (0.97–0.99) and 0.95 (0.90–0.99), respectively. However, the lower ORs for habitual bruxism were additive with longer sleep duration at 6 months of age in the control group but not in participants with ASD. Additionally, the association between sleep duration at later time points, from 12 to 36 months of age, and habitual bruxism was not significant (S2 Table).”

#9

The following two comments about the previous studies seemed evoke doubt on the novelty of this study. The authors should provide more detailed explanation how the findings of this study relate to those of previous studies.

P16L232 “the crude and adjusted ORs for habitual bruxism behavior consistently decreased with longer sleep duration at 1 month of age, similar to our latest report [10].”

P18L250 “We found that the occurrence of habitual bruxism was higher in children with ASD than in those with typical development, which is consistent with the findings of a systematic review of case-controlled trials by [17]”

#10

P19L277 ASD-related bruxism

Please explain if ASD-related bruxism is an official name of classification of bruxism? Does it refer to one of secondary bruxism?

Conclusion

#11

The novelty in the following simple conclusions is difficult for readers to understand. More adequate expression of explanation is considered to be needed as conclusion.

P21L301 “The risk of developing habitual bruxism is higher in children with ASD than those without the disorder and is associated with shorter sleep duration in the neonatal period.”

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2024 Dec 6;19(12):e0313024. doi: 10.1371/journal.pone.0313024.r003

Author response to Decision Letter 0


16 Jul 2024

PONE-D-24-13310

Title: Behavioral occurrence of bruxism in children with autism spectrum disorder:the Japan Environment and Children's Study (JECS)

Authors: Masahiro Tsuchiya, Shinobu Tsuchiya, Haruki Momma, Ryoichi Nagatomi, Nobuo Yaegashi, Takahiro Arima, Chiharu Ota, Kaoru Igarashi, and the Japan Environment and Children’s Study Group.

Dear Dr. Ayako Mochizuki, DDS, PhD.

Academic Editor in PLOS ONE

We wish to thank the editor and reviewers for carefully reading our manuscript and providing detailed comments and suggestions, which have helped improve the manuscript. We have considered them and have revised the manuscript accordingly. Our changes are shown in red. Point-by-point answers to the comments of the editor and reviewers are in bold below:

Reviewer #1: In this study, a dataset (n = 83,720) obtained from the Japan Environment and Children's Study (JECS), a nationwide birth cohort study was subjected to multiple imputation for verifying an increased prevalence rate of bruxism behavior in children with ASD. Additionally, the association between habitual bruxism in participants with ASD and sleep duration in infants on bruxism was examined using logistic regression analysis with adjustments for several maternal and child-related variables. The prevalence of ASD and habitual bruxism was 1.2% and 7.2%, respectively. The odds ratio of the increased risk of bruxism in individuals with ASD (95% confidence interval) was 1.59 (1.31–1.94) after covariate adjustments. Furthermore, a longer sleep duration in the neonatal period was significantly associated with a decreased risk of habitual bruxism in participants with ASD. The results of this study show that habitual bruxism is highly prevalent among children with ASD and is associated with sleep duration, particularly in the neonatal stage. The results of this study are interesting, and this article is well written. However, the following minor concerns should be addressed.

We are grateful for your careful review of our manuscript and useful comments, which helped us address the concerns raised with the appropriate corrections and revisions. We have considered your suggestions and revised the manuscript accordingly.

1) Emerging evidences suggest that dysbiosis of gut microbiota plays a role in ASD, and that oral microbiota may in part be regulated by gut microbiota. Please discuss a potential role of dysbiosis in oral microbiota and subsequent poor oral care in bruxism of ASD children.

A hypothesis of dysbiosis in children with ASD should be interesting for readers. Following the suggestion from reviewer #1, we added the relevant points to the Discussion section (P19L303–P21L307).

2) Table 1: Prevalence of ASD in boy is higher than that of girl. is there a significant gender difference in bruxism in this study?

In the JECS dataset, the prevalence of bruxism behavior in male participants was higher than in females (8.1% vs 6.2% in females), and the OR (95% CI) of bruxism behavior in males was 1.32 (1.25–1.39, p <0.001) in the adjusted model for all covariates. Because the results definitively depend upon the diagnostic criteria and study designs, the sex-based difference in bruxism behavior remains controversial. Several reports show a dominant prevalence of bruxism behavior in males (Lam MH, et al., Sleep Med. 2011;12:641-5; Insana SP, et al, Sleep Med. 2013;14:183-8; de Almeida AB, et al., Int J Environ Res Public Health. 2022;19(13):7823), in female (Serra-Negra JM, et al., Eur Arch Paediatr Dent. 2010;11(4):192–195.; Seraj B, et al., Iran J Pediatr. 2010 Jun; 20(2): 174–180.; Alves CL, Sleep Sci. 2019; 12(3): 185–189.), and no differences (Fonseca CM, et al., Sleep Breath. 2011;15(2):215–220.). Of these studies, Lam et al. (Sleep Med. 2011;12:641-5), based on a multivariate logistic regression analysis, indicated an increased OR for bruxism behavior in males (OR [95% CI] = 1.69 [1.37–2.10], p <0.001).

Thus, the above descriptions have been summarized in the Results and Discussion sections to ensure clarity in sex-based differences in bruxism behavior (P13L213–214; P19L292–301).

Overall, this study was conducted well, and this article is interesting.

We thank Reviewer #1 for the careful review and structural suggestions, which have helped us improve the manuscript.

Reviewer #2: [General comments]

This study attempted to examine the increased prevalence of bruxism in children with ASD, and the relationship between the prevalence of bruxism and sleep duration in infants. The objective of the study was vague, the expression of novelty in the introduction and discussion is unclear, and the differences with the results of the previous papers are unclear. Furthermore, the definition of bruxism was not explained sufficiently. Bruxism was assessed solely through a questionnaire, but the diagnostic validity of this is questionable. Without sufficient explanation and improvements on these critical points, it is difficult to recommend this paper for publication in PLOS ONE.

We thank Reviewer #2 for the careful review, detailed comments, and structural suggestions, which have helped us to improve the quality of the manuscript. We have accepted all of the suggestions for revision and thoroughly made appropriate changes throughout the manuscript, to ensure clarity for the journal’s readers. Specifically, the study’s purpose (P3L40–42 in abstract; P5L80–P6L87), the novel findings in our research (P3L45–L49 in abstract; P17L253–258; P21L325–326), the definition of bruxism (P4L51–53; P7L120–P8L122), and the study’s limitation related to the diagnostic validity of bruxism by the questionnaire (P20L313–P21L322) have been described under appropriate sections of the manuscript. We hope that the revised manuscript is deemed suitable for publication in PLOS ONE.

Introduction

#1

The authors should clarify what had not been clarified in the previous researches and mention specifically which part of the characteristics of the relation between bruxism and ASD was tried to clarify in this research. More clear statement on objectives is needed. It is probably better method to present a specific hypothesis.

We appreciate your structural comments. Severe bruxism is commonly observed in children with ASD and is considered a major oral health concern damaging orofacial tissues such as teeth, periodontium, and temporomandibular joints. A recent systematic review by Granja (Spec Care Dentist. 2022;42(5):476-485) reported that bruxism’s prevalence is approximately four times higher among individuals with ASD (P4L61–62). Since the association between a higher occurrence of bruxism and ASD has been acknowledged, we focused on the additive interaction between infant sleep duration and the occurrence of bruxism among children with ASD as a specific hypothesis in this manuscript (P5L84 – P6L87).

#2

Is the bruxism in ASD patients classified as secondary bruxism (symptomatic bruxism)?

It should be stated how the previous studies dealt with and how the authors had recognized for conducting this study.

As pointed out by Reviewer #2, bruxism is distinguished as primary or secondary based on the association with other underlying diseases (Bulanda S, et al. Int J Environ Res Public Health. 2021;18(18):9544). Thus, bruxism behavior observed in patients with ASD is categorized as secondary bruxism (symptomatic bruxism). In agreement with your suggestion, we stated the detailed definition of bruxism involving the classification in the Introduction (P4L58–L61).

#3

In the introduction part, some comments on drug-induced factors on ASD and bruxism should also be described.

We appreciate your pertinent comment. de Baat et al. summarized ASD medications potentially aggravating bruxism behavior (J Oral Rehabil. 2021;48:343-354.). According to your suggestion, we added this information in the Introduction (P4L62–L65). The characteristics of participants, mostly young, before the start of ASD medication, have been described in the section of the study limitation (P18L282–P19L291).

#4 It should also be made clear whether the bruxism objected in this study is sleep bruxism and/or awake bruxism.

We are grateful for your careful review of our manuscript. The bruxism behavior is distinguished into two circadian symptoms: sleep and awake (P4L51–L53; P20L316–L320), as pointed out by Reviewer #2. Regarding the main study limitation, the dataset did not include enough information on bruxism behavior observed during sleep/awake status. Although further studies with detailed estimation of bruxism behavior in children with ASD are warranted, it should be noted that Winocur and his colleagues previously observed a higher concordance of both sleep and awake bruxism at an interindividual level (Front Neurol 2019;10:443.). We added the above including the reference under limitations in the revised manuscript (P20L313–P21L322).

Methods

#5

A clear definition of "bruxism" should be presented. Further, the definition of "habitual bruxism" should be made clear in terms of definitions in previous studies, definitions at international conferences etc. In addition, the local definition of "bruxism" within this paper and the reason for adopt the definition should also be stated.

We appreciate your valuable comment to improve the manuscript. First, according to the international consensus on bruxism definition (Lobbezoo F, Ahlberg J, Raphael KG, et al. International consensus on the assessment of bruxism: Report of a work in progress. J Oral Rehabil. 2018;45:837-844.), the definition in the Abstract and Introduction has been corrected (P3L34-35 in Abstract; P4L51–53).

We changed the term “habitual bruxism” to “bruxism behavior” throughout the manuscript for ease of understanding of our findings for readers and reviewers. Additionally, in terms of the definition for the local definition of “bruxism behavior” in this study, considering that consistent bruxism behavior increases a risk for dental tissue damage, participants with “bruxism behavior” observed at both time points (2 and 4 years of age) were categorized into the bruxism group throughout the manuscript. To help readers understand better, we have added a clear categorization explaining the above in the Methods section (P7L117–P8L124).

#6

It is necessary to provide a detailed explanation of the method for assessing bruxism. The contents of the reference studies should also be explained. The validity of diagnosing by interview alone should be discussed in the method part and/or the discussion part. This might had better be added as a limitation in the discussion part.

We are grateful for your careful reading of the manuscript and structural suggestions. Since the data collection methods in this study did not include a query about the diagnostic validity and classification of bruxism behavior, the assessment of a child's bruxism behavior only using the parental-report questionnaire should be considered as a major study limitation. For example, a direct measure, such as electromyography for estimating sleep bruxism would provide more accurate data in sleep-wake cycles. In contrast, it would not be favorable for a large-scale cohort study in early childhood like in this study. Conclusively, further studies with detailed estimation of bruxism behavior in children with ASD are warranted. In agreement with your point, we added and revised the sentences explaining the above under limitations in the Discussion section (P20L313–P21L322).

Results

#7

The following items should be written in more understandable manner: 1. The relationship between sleep duration and the prevalence of bruxism, 2. The relationship between ASD and the prevalence of bruxism, and 3. Whether the influence of sleep duration is greater in ASD patients than in controls.

Thank you for your valuable comment. We revised the Result section according to your comment above.

The OR (95% CIs) for “1. the relationship between sleep duration and the prevalence of bruxism” was 0.98 (0.97–0.99) per hour increase. However, since it is consistent with our previous study (Tsuchiya et al., Sleep Med. 2022:100:71-78.), it is stated on P15L223–224. For “2. The relationship between ASD and the prevalence of bruxism,” the OR (95% CIs) was 1.59 [1.31–1.94] as described on P15L221-223 and Table 2.

“3. Whether the influence of sleep duration is greater in ASD patients than in controls” was additionally examined and indicated in Figure 2. Regarding the interaction between ASD prevalence and the shortest sleep duration at 1 month of age (≤13) on bruxism behavior, short sleep duration (1.17 [1.10–1.25], p <0.001) and prevalence of ASD (1.38 [1.08–1.78], p = 0.012) were associated with increased ORs (95% CIs) for bruxism behavior in the adjusted model for all covariates. Further, the OR (95% CIs) for bruxism behavior in ASD participants having short sleep duration was 2.46 (1.80–3.38, p <0.001) (Figure 2). Furthermore, a significant interaction between ASD and short sleep duration was observed (1.52 [1.02–2.23], p <0.05).” Thus, in agreement with your suggestion, the above description has been newly included in the Result section (P16L238– 246).

#8

P15L218

It is questionable whether the following sentences can explain the characteristic that bruxism of individuals with ASD are more susceptible to the influences of sleep duration than controls.

“The ORs (95%CIs) for habitual bruxism per hour increase of sleep duration in the control and ASD groups were 0.98 (0.97–0.99) and 0.95 (0.90–0.99), respectively. However, the lower ORs for habitual bruxism were additive with longer sleep duration at 6 months of age in the control group but not in participants with ASD. Additionally, the association between sleep duration at later time points, from 12 to 36 months of age, and habitual bruxism was not significant (S2 Table).”

We thank Reviewer #2 for the structural suggestions, which have helped us improve the manuscript. As you pointed out, these sentences can cause misunderstanding for readers. After analyzing the interaction between infants’ sleep duration and ASD prevalence, we revised the description and added Figure 2 as described in our response to comment #7 (P16L238– 246).

#9

The following two comments about the previous studies seemed evoke doubt on the novelty of this study. The authors should provide more detailed explanation how the findings of this study relate to those of previous studies.

P16L232 “the crude and adjusted ORs for habitual bruxism behavior consistently decreased with longer sleep duration at 1 month of age, similar to our latest report [10].”

P18L250 “We found that the occurrence of habitual bruxism was higher in children with ASD than in those with typical development, which is consistent with the findings of a systematic review of case-controlled trials by [17]”

We understand the reviewer’s argument that the sentences were vague. Thus, we have rewritten them (P16L233–237; P17L253–256).

#10

P19L277 ASD-related bruxism

Please explain if ASD-related bruxism is an official name of classification of bruxism? Does it refer to one of secondary bruxism?

Bruxism observed in patients with ASD is categorized as secondary as described in response to #2. In accordance with the suggestions, the term “ASD-related bruxism” has been revised to “bruxism behavior in patients with ASD” (P4L61–65; P19L301).

Conclusion

#11

The novelty in the following simple conclusions is difficult for readers to understand. More adequate expression of explanation is considered to be needed as conclusion.

P21L301 “The risk of developing habitual bruxism is higher in children with ASD than those without the disorder and is associated with shorter sleep duration in the neonatal period.”

The Conclusion has been revised as per your suggestions (P21L325–326).

We again thank the reviewers for providing insightful comments.

Decision Letter 1

Ayako Mochizuki

15 Aug 2024

PONE-D-24-13310R1Behavioral occurrence of bruxism in children with autism spectrum disorder:the Japan Environment and Children's StudyPLOS ONE

Dear Dr. Tsuchiya,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Academic Editor

PLOS ONE

Additional Editor Comments:

Your paper has been reviewed. The comments of the reviewers are included at the bottom of this letter.

The reviewers have recommended major revisions to your manuscript. Therefore, I invite you to revise and resubmit your manuscript as fast as possible.

Please carefully address the issues raised in the comments.

Kind regards,

Ayako Mochizuki

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: My all comments have been addressed. The authors addressed all comments. I have no additional comments.

Reviewer #2: [General comment]

Although the issues raised by Reviewers have been somewhat improved, a more appropriate explanation based on deeper understanding of bruxism is necessary.

[Detailed concerns]

1)”bruxism behavior”

------------The authors are responsible for accurately defining the extent and characteristics of the study participants.

The subjects in this study were bruxers that were determined by whether or not they were aware of their bruxism based on report by their parents.

More specifically, the subjects in this study were child bruxers whose parents answered "Yes" to the question, "Does your child have bruxism?" at the ages of 2 and 4.

First of all, this should be clearly stated and appropriate group name (i.e., abbreviation) for the subject group specific to this study should be defined.

Bruxism is a diagnostic term, and the expression "bruxism behavior" is inappropriate because it leads readers to imagine a specific type of bruxism and confuses them. Use of "bruxism behavior" cannot be acceptable.

2)The reply from the author ”in terms of the definition for the local definition of “bruxism behavior” in this study, considering that consistent bruxism behavior increases a risk for dental tissue damage, participants with “bruxism behavior” observed at both time points (2 and 4 years of age) were categorized into the bruxism group throughout the manuscript.”

---------- Since basis and meaning of this theory are unclear, the sentences cannot be acceptable.

3)The question "Does your child have Bruxism?"

-----------What does the question "Does your child have Bruxism?" mean?

Does this question refer to grinding, clenching, during sleep, or during awake state, or include all of them?

More information and explanation are needed in the Methods and Discussion parts regarding the meaning of this question wording.

4)The reply from the author ”The bruxism behavior is distinguished into two circadian symptoms: sleep and awake (P4L51–L53; P20L316–L320), as pointed out by Reviewer #2. Regarding the main study limitation, the dataset did not include enough information on bruxism behavior observed during sleep/awake status. Although further studies with detailed estimation of bruxism behavior in children with ASD are warranted, it should be noted that Winocur and his colleagues previously observed a higher concordance of both sleep and awake bruxism at an interindividual level (Front Neurol 2019;10:443.). We added the above including the reference under limitations in the revised manuscript (P20L313–P21L322).”

------This reply does not address the reviewer's point that asked for clarification regarding the type of bruxism that was the subject of this study.

It should be more clearly stated in the Introduction and Methods parts whether the bruxism studied in this study was sleep bruxism or awake bruxism.

I cannot understand the intention behind suddenly citing only the paper by Winocur's group. The paper by Winocur's group assessed bruxism based only on simple questions. It is already known that questionnaires do not have a high accuracy rate for either SB or AB.

In particular, recent studies have shown that AB cannot be judged by questionnaire based on self-awareness (Ishimaru, J Prosthodont Res. 2024). In addition, a study that evaluated SB with higher reliability using electromyograms instead of questionnaires found no correlation between SB and AB at all (Mikami, J Prosthodont Res. 2024).

This paper should more clearly state its inability to distinguish between SB and AB as its limitations.

**********

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PLoS One. 2024 Dec 6;19(12):e0313024. doi: 10.1371/journal.pone.0313024.r005

Author response to Decision Letter 1


10 Sep 2024

PONE-D-24-13310

Title: Bruxism associated with short sleep duration in children with autism spectrum disorder: the Japan Environment and Children's Study

Authors: Masahiro Tsuchiya, Shinobu Tsuchiya, Haruki Momma, Ryoichi Nagatomi, Nobuo Yaegashi, Takahiro Arima, Chiharu Ota, Kaoru Igarashi, and the Japan Environment and Children’s Study Group.

Dear Dr. Ayako Mochizuki, DDS, PhD.

Academic Editor in PLOS ONE

We thank the editor and reviewers for repeatedly reading our manuscript and providing structural suggestions, which have helped improve the manuscript. We have considered these suggestions and have revised the manuscript accordingly. Our changes in the manuscript are shown in red. The point-by-point answers to the comments of the editor and reviewers are presented in bold below:

Reviewer #1: My all comments have been addressed. The authors addressed all comments. I have no additional comments.

We thank you for the thoughtful review of our manuscript and useful comments, which have helped us address the concerns raised with appropriate corrections and revisions.

Reviewer #2:

Although the issues raised by Reviewers have been somewhat improved, a more appropriate explanation based on deeper understanding of bruxism is necessary.

We thank you for carefully reviewing our manuscript and providing constructive suggestions, which have helped us in revising it appropriately. We have considered your suggestions related to the inappropriate definition of bruxism observed in the study participants. We have accordingly modified the relevant sentences in the text.

1)”bruxism behavior”

------------The authors are responsible for accurately defining the extent and characteristics of the study participants.

The subjects in this study were bruxers that were determined by whether or not they were aware of their bruxism based on report by their parents. More specifically, the subjects in this study were child bruxers whose parents answered "Yes" to the question, "Does your child have bruxism?" at the ages of 2 and 4. First of all, this should be clearly stated and appropriate group name (i.e., abbreviation) for the subject group specific to this study should be defined. Bruxism is a diagnostic term, and the expression "bruxism behavior" is inappropriate because it leads readers to imagine a specific type of bruxism and confuses them. Use of "bruxism behavior" cannot be acceptable.

As pointed out, the study participants were defined as those with parent-reported bruxism for readers’ ease of understanding. We believe that a consistent prevalence of parent-reported bruxism will improve research reproducibility when a parent-administered questionnaire is used for examining the prevalence of bruxism. Thus, we have included participants with bruxism observed by the parents at both time points (2 and 4 years of age) in the PRB group and have changed the term “bruxism behavior” to “parent-reported bruxism (PRB)” throughout the manuscript to avoid misunderstanding.

As we have added the above description in the Methods (page 7, line 121–page 8, line 128), we hope that the term, “parent-reported bruxism”, observed in the participants, and its abbreviation, “PRB”, would address your concerns. Please let us know if issues regarding the handling of this term and its abbreviation persist in the revised manuscript such that we can address them suitably.

2) The reply from the author ”in terms of the definition for the local definition of “bruxism behavior” in this study, considering that consistent bruxism behavior increases a risk for dental tissue damage, participants with “bruxism behavior” observed at both time points (2 and 4 years of age) were categorized into the bruxism group throughout the manuscript.”

---------- Since basis and meaning of this theory are unclear, the sentences cannot be acceptable.

We agree with you that the previous theory explaining the categorization method of parent-reported bruxism was not sufficient in terms of the basis and meaning of the theory. In accordance with your suggestion, we have revised the relevant points in the Methods (page 8, line 124–line 126).

3)The question "Does your child have Bruxism?"

-----------What does the question "Does your child have Bruxism?" mean?

Does this question refer to, or include all of them? More information and explanation are needed in the Methods and Discussion parts regarding the meaning of this question wording.

We understand your argument that the question “Does your child have bruxism?” was vague; however, unfortunately, the questionnaire did not include other information on bruxism observed by the parents. Therefore, our findings included all types and severities of bruxism, for example, grinding and clenching both in the and sleep/awake states, as you have pointed out. Thus, per your suggestion, we have provided further information and explanation in the Methods and Discussion (page 7, line 121–line 128; page 20, line 317–line 322).

4)The reply from the author ”The bruxism behavior is distinguished into two circadian symptoms: sleep and awake (P4L51–L53; P20L316–L320), as pointed out by Reviewer #2. Regarding the main study limitation, the dataset did not include enough information on bruxism behavior observed during sleep/awake status. Although further studies with detailed estimation of bruxism behavior in children with ASD are warranted, it should be noted that Winocur and his colleagues previously observed a higher concordance of both sleep and awake bruxism at an interindividual level (Front Neurol 2019;10:443.). We added the above including the reference under limitations in the revised manuscript (P20L313–P21L322).”

----- -This reply does not address the reviewer's point that asked for clarification regarding the type of bruxism that was the subject of this study.

It should be more clearly stated in the Introduction and Methods parts whether the bruxism studied in this study was sleep bruxism or awake bruxism.

I cannot understand the intention behind suddenly citing only the paper by Winocur's group. The paper by Winocur's group assessed bruxism based only on simple questions. It is already known that questionnaires do not have a high accuracy rate for either SB or AB.

In particular, recent studies have shown that AB cannot be judged by questionnaire based on self-awareness (Ishimaru, J Prosthodont Res. 2024). In addition, a study that evaluated SB with higher reliability using electromyograms instead of questionnaires found no correlation between SB and AB at all (Mikami, J Prosthodont Res. 2024).

This paper should more clearly state its inability to distinguish between SB and AB as its limitations.

We appreciate your suggestions. The type of bruxism (e.g. sleep or awake bruxism) must be clearly noted. However, the question used in the study could not definitively distinguish the bruxism type into sleep and awake states. Additionally, as suggested, the low accuracy rates for assessing sleep/awake bruxism in studies using questionnaires have been mentioned (Ishimaru et al, J Prosthodont Res. 2024; Mikami et al, J Prosthodont Res. 2024). Following your suggestion, we have revised the relevant points in the Discussion, citing the above references (page 20, line 317–page 21, line 324).

We again thank the reviewer #2 for your careful reading of the manuscript and their appropriate opinions. We have considered your suggestions and revised the manuscript accordingly.

Attachment

Submitted filename: Responses_to_Reviewers_PONE-D-24-13310_R2.docx

pone.0313024.s005.docx (43.6KB, docx)

Decision Letter 2

Ayako Mochizuki

17 Oct 2024

Bruxism associated with short sleep duration in children with autism spectrum disorder:the Japan Environment and Children's Study

PONE-D-24-13310R2

Dear Dr. Masahiro Tsuchiya,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Ayako Mochizuki

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I am glad to say that reviewers and I are satisfied with your manuscript and have decided that it is appropriate to publish it in PLOS ONE. Congratulations on your excellent work!

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: (No Response)

Reviewer #3: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: After reviewing your manuscript, I am pleased to inform you that I found no significant issues. The work is well-structured and contributes meaningfully to the field.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

Acceptance letter

Ayako Mochizuki

28 Nov 2024

PONE-D-24-13310R2

PLOS ONE

Dear Dr. Tsuchiya,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Text. STROBE statement.

    (DOCX)

    pone.0313024.s001.docx (36KB, docx)
    S1 Table. Baseline association of sleep duration with the prevalence of PRB in 83,720 children.

    (DOCX)

    pone.0313024.s002.docx (38.6KB, docx)
    S2 Table. Association of sleep duration with the prevalence of PRB in infants with or without ASD.

    (DOCX)

    pone.0313024.s003.docx (52.9KB, docx)
    Attachment

    Submitted filename: Response letter_PONE-D-24-13310.docx

    pone.0313024.s004.docx (29.1KB, docx)
    Attachment

    Submitted filename: Responses_to_Reviewers_PONE-D-24-13310_R2.docx

    pone.0313024.s005.docx (43.6KB, docx)

    Data Availability Statement

    Data are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Medical and Health Research Involving Human Subjects enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restricts the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.


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