The sleep-anxiety-cancer triad in pediatrics: Unraveling a vicious cycle

The sleep-anxiety-cancer triad in pediatrics: Unraveling a vicious cycle | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The sleep-anxiety-cancer triad in pediatrics: Unraveling a vicious cycle Atbin Latifi Kasani, Mohaddese Mohammad Salehi, Majid Taheri, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7420057/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Background Sleep disorders in children are associated with developmental and cognitive impairments, but their interaction with cancer has been unclear in previous studies. This cross-sectional study was conducted to investigate the association between sleep disorders in children with cancer and their impact on anxiety in these children. Methods The present study examined children with various types of cancer who were referred to Amir Kabir Hospital, Markazi Province, Iran, over a 6-month period, using the Spence Children's Anxiety Questionnaire (SCAS) and the Children's Sleep Disorders Questionnaire (CSHQ). Children underwent anthropometric examinations, and child weight, child height, child head circumference, body mass index, weight-for-height ratio (wasting), height-for-age ratio (nutritional short stature), and weight-for-age ratio (underweight) were statistically analyzed along with sleep and anxiety scores. Results The mean total sleep disorder score among these children was 26.55, and the mean anxiety score among children was 34.74. A direct relationship was observed between anxiety and delayed sleep onset, an inverse relationship with parasomnia, and a direct and significant relationship with daytime sleepiness. A positive correlation was found between sleep disorders and cancer type and chemotherapy, and a negative correlation was observed between anxiety and chemotherapy and relapse. Conclusion Sleep disturbance associated with cancer can increase anxiety, creating a cycle that may worsen cancer-related factors. This cycle can lead to lower treatment effectiveness in children. The obtained evidence suggests that managing sleep disorders may be a crucial first step in breaking this cycle. Sleep disorders Anxiety Cancer Children chemotherapy Figures Figure 1 Introduction Sleep disorders that postpone children’s growth process could change brain structure and reduce network efficacy ( 1 ). Improving brain functions and nerve pathways is linked to treatment opportunities focusing on sleep duration and quality, specifically in children. Prioritizing quality sleep in pediatrics is essential, as inadequate sleep duration and poor sleep quality can negatively affect cognitive and emotional functions ( 2 , 3 ), as well as direct immunological pathways to control inflammation ( 4 ). As Interleukin-6(IL-6) and C reactive protein (CRP) increase in sleep disturbance ( 5 ), cancer-related cytokines and their signaling pathways, even radiotherapy efficacy, aliterate by sleep quality distraction ( 6 ). Pioneering medicine should change its vision of sleep to a therapeutic procedure, particularly as therapeutic choices are at risk of anxiety and stress. Proinflammatory and tumor factors change through anxiety and stress that parallel the worst therapeutic results ( 7 ). Anxiety reduces immunological potency ( 8 ) and increases levels of TNF-a and IL-6, which are key cytokines involved in the development of cancer ( 9 ). As a result, incorporating meditation and relaxation techniques into treatment plans is now considered an essential aspect of cancer therapy. Patients under chemo or radiotherapies usually show stress and anxiety by losing treatment effectiveness and rehabilitation ratio ( 10 , 11 ). Whether children with normal sleep show lower anxiety levels ( 12 ), the ambiguity of sleep disturbance level correlation with anxiety levels is unclear. This investigation gathered children who suffered from cancer to terminate arguments about the correlation between sleep disturbance, anxiety, and cancer in children. Methods Study oversight This study was conducted as a cross-sectional analysis at the Arak University of Science and Medical Sciences, Arak, Iran, with the approval of the Arak medical science university's ethics committee, to elucidate sleep disorders in children afflicted with cancer. Children referred to Amir Kabir Hospital who were experiencing sleep disorders were compared with control groups. Participants were recruited from children referred between September 2022 and March 2023, with parents responding to inquiries regarding sleep disorders. Informed consent was obtained in line with the Hilinski Declaration and the standards for Legally Authorized Representatives (LAR). This manuscript is structured according to the STROBE checklist. Participant A pediatric physician assessed children up to 15 years old diagnosed with cancer to assess sleep disorders based on the American Academy of Sleep Medicine (AASM) guideline specialized for pediatrics (Fig. 1 ). The diagnosis of cancer and its types were reviewed based on symptoms and final confirmation by a pediatric oncologist. Mothers were also assured that their children's details would remain confidential to the researchers. A profile was created for each child, including demographic and sleep disorder test results, anxiety results, cancer type, and anthropometric data. The specialist physician assessed the anthropometry index for every patient, and the Children's Sleep Habits Questionnaire measured sleep disorders. Mothers answered the questions with the support of an impartial interviewer familiar with the questionnaire. Ultimately, the interviewer finalized a checklist that encompassed demographic and age-related details, such as the child's age in months, gender, birth order, aspirations of the child, the count of children under six years old, as well as the employment and educational background of the parents, household size, housing conditions regarding infrastructure quality, type of home ownership, ethnicity, and religious affiliation. Children's Sleep Disorders Questionnaire (CSHQ) The Children's Sleep Disorders Questionnaire (CSHQ) was used to measure children's sleep patterns over the past two weeks. It is designed for children 4 to 12 years of age and provides a broad description of children's sleep patterns. The CSHQ yields a total sleep disorder score and is measured for eight scales (resistance to sleep onset, sleep onset delay, sleep duration, sleep anxiety, nighttime awakenings, parasomnias, sleep-disordered breathing, and daytime sleepiness). Internal consistency measures for the entire scale are high (α = 0.68 among a community sample, α = 0.78 among a clinical sample), and test-retest reliability across scales is high (r = 0.62 to 0.79). A CSHQ total score ≥ 41 has a sensitivity and specificity of 0.80 and 0.72, respectively, correctly classifying 80% of the population with clinically relevant sleep disorders. This questionnaire was completed under the supervision of an impartial interviewer knowledgeable about the questionnaire to ensure uniform and complete completion. This questionnaire consists of 33 multiple-choice items and provides information about nighttime sleep hours, wakefulness patterns, daytime sleepiness, and similar factors from the previous week. This questionnaire consisted of eight subscales as follows: Bedtime resistance (items 1, 3, 4, 5, 6, 8) Sleep onset delay (item 2) Sleep duration (items 9, 10, 11) Sleep disturbance (items 5, 7, 8, 21) Nighttime awakenings (items 16, 24, 25) Parasomnias (items 12, 13, 14, 15, 17, 22, 23) Sleep-disordered breathing (items 18, 19, 20) Daytime sleepiness (items 26–33). The items are scored on a Likert scale (usually, sometimes, rarely) from 1 to 3. Thus, if the behavior is repeated 5–7 days a week, the option is usually marked (score 3), 2–4 times a week, the option is sometimes marked (score 2), and 0–1 times a week, the option is rarely marked (score 1). Items 1-2-3-1011-26 are inverted. The scoring method of the tool is such that the higher the full score obtained from the tool, the more inappropriate the child's sleep situation is. The minimum and maximum scores of this questionnaire are 33 and 99. Anxiety scale The Spence Child Anxiety Inventory (SCAS) was used to measure child anxiety. This scale is one of the most widely used tools in assessing anxiety symptom dimensions. The parent answering form of this scale had 38 items and was rated on a Likert scale from 0 (never) to 3 (always), with the highest score being 114. This scale assessed anxiety symptoms in six subtypes: Separation anxiety, social phobia/agoraphobia, generalized anxiety, specific phobia, fear of injury, and obsessive-compulsive disorder. This questionnaire has acceptable internal consistency (Cronbach's alpha 89%). The reliability and validity of the Japanese version of this scale have also been reported to be satisfactory. Anthropometric assessments Information such as children's weight, height, head circumference, body mass index (BMI), and anthropometric data was obtained by a specialist physician using common indicators to determine children's nutritional status, including weight-for-height (wasting), height-for-age (nutritional stunting), and weight-for-age (underweight), by comparing them with standard tables from the World Health Organization and based on Z-Score. Statistical analysis The research data were entered into SPSS software version 18 for data analysis. Descriptive statistics characterized and presented the types of sleep disorders by frequency tables. The associations of the sleep disorders with the variables under consideration were evaluated using logistic regression analysis, independent t-test analysis, and a chi-square (χ²) test. A normality test was performed to evaluate the normality of the data. The data were analyzed based on the normality assessment results. For normally distributed data, independent t-tests were employed to compare the continuous variables in case and control groups. The Kolmogorov-Smirnov test confirmed the distribution of the data, thus aiding the selection of appropriate statistical methods. Categorical variables, such as demographic characteristics (gender, parental education, and environmental tobacco smoke exposure), as well as several sleep disorders, were subjected to chi-square (χ²) tests for significant association. This study conducted logistic regression analyses to explore how various independent variables such as demographic factors, body measurements, and environmental exposure impact sleep disorders in children. These analyses accounted for potential confounding factors to ensure accurate results. All the statistical tests were carried out at significance level α = 0.05 and power = 80% β = 0.20. Previous studies-derived odds ratio (OR) (2.14 = OR) has been used for calculating sample size. Based on these, the required sample size was 212 participants ( 13 ). Results Participants The present study assessed 212 children (age mean: 7.29 ± 2.6 years old) who suffered from leukemia, lymphoma, and malformation. ALL in leukemia and non-Hodgkin in lymphoma types had the most distribution. Less than 10% were in stage one or four, and 16.4% had a recurrence, and they were under surgery, radiotherapy, and chemotherapy (Table 1 ). More than half of mothers had a diploma or lower education level, compared to only 45.8% of fathers with bachelor's degrees. Before pregnancy, 11.3% of mothers smoked, with only 1.4% smoking more than 10 cigarettes daily, and many reduced their smoking during breastfeeding. During this period, only 3.8% of mothers continued to smoke. Moreover, 23.5% of mothers were exposed to secondhand smoke from fathers, creating a passive smoking environment before pregnancy (Table 2 ). The total sleep score did not change significantly based on the anxiety score Dependency of anxiety and total sleep disorders mark did not significantly, even though the studied children showed high levels in both of these variables. Daytime sleepiness and delayed sleep onset were both directly affected by anxiety scores, while resistance to going to bed, parasomnias, and sleep disturbance were inversely affected by anxiety scores (Table 3 ). Sleep disorders were directly related to the child's height and inversely related to the child's head circumference and the mother's occupation. Anxiety was directly related to the child's age and inversely related to the father's education (Table 4 ). Sleep disturbances vary depending on the type of cancer Cancer stages, surgery treatments, and cancer recurrence do not change total sleep disorders; however, cancer type and chemotherapy could directly change this mark level. Radiotherapy was inversely associated with the total sleep disturbance score, associated with the children's overall sleep hygiene. Children who were undertreated by chemotherapy had lower anxiety marks, and this inverse ratio is also visible in recurrence (Table 4 ). Discussion The average of anxiety, sleep disorders, and its dimensions showed that the average total score of sleep disorders among these children was 26.55. The lowest rate of sleep disorders was 38%, and the highest rate was 82%. Furthermore, the lowest anxiety score was 58, and the highest rate was 100, indicating a high proportion of sleep disorders and anxiety among these children. The findings indicate a direct relationship between anxiety and delayed sleep onset, an inverse relationship with parasomnia, and a direct and significant relationship with daytime sleepiness. A positive correlation was found between sleep disorders and chemotherapy and the type of cancer. Additionally, a negative correlation was observed between anxiety, chemotherapy, and recurrence. Each of the components of the disorder, such as pain, BMI, and physical activity limitations, may serve as a modifiable target for interventions to improve sleep quality in patients and survivors ( 14 , 15 ). The impact on Hodgkin lymphoma (HL) survivors was similar to that in obese survivors of CNS tumors ( 16 ), with higher BMI scores associated with higher risks of sleep problems. This suggests that BMI is a predictive factor that influences sleep quality in lymphoma survivors and may be interpreted as a cause of sleep disturbance in other survivors ( 17 ), regardless of cancer type. Sleep disturbances were directly associated with child height and inversely associated with child head circumference, maternal occupation, and income ( 18 , 19 ). The course of cancer and subsequent elective treatments are linked to changes in anthropometric indices, specifically in children, where these indices reflect growth status ( 20 ). The obtained findings indicate that weight loss during cancer treatment is linked to higher rates of sleep and anxiety disorders( 21 ). During childhood leukemia treatment, the child's mood, coping skills, and self-soothing skills are affected by the cancer diagnosis ( 22 ), leading to increased psychological distress, which is crucial to examine, given that depression or clinical anxiety is reported in approximately one-quarter of pediatric cancer patients and survivors ( 23 , 24 ). Insomnia is one of the most common sleep problems that have a strong bidirectional relationship with anxiety, a phenomenon that is also observed in childhood leukemia survivors( 25 ). Adult survivors of childhood cancer who suffer from insomnia often experience heightened anxiety. Depression in childhood cancer survivors leads to an increased prevalence of sleep problems, such as increased excessive daytime sleepiness (EDS). When analyzing the reciprocal effect of sleep and mood disorders, a vicious cycle emerges in which sleep disorders can be both a cause and a consequence of psychological distress. Mood, behavior, and the patient's and caregiver's inherent psychological predisposition play an essential role in sleep ( 26 , 27 ). Therefore, addressing these interconnected and multifactorial causes is significant to breaking the sleep and mood disorders cycle. The conflicting data on sleep in leukemia survivors lack satisfactory explanations and highlight the need for further research to uncover fundamental changes in sleep. The obtained results clearly show that the type of cancer is associated with an overall score of sleep disorders, and chemotherapy is also associated with higher levels of sleep disorders. When choosing a treatment, it should be kept in mind that chemotherapy may increase sleep disorders and worsen treatment outcomes. On the other hand, chemotherapy is associated with a lower chance of anxiety, which may be a result of the familiarity of the patient community with chemotherapy and their adaptation to this type of treatment. Radiotherapy may slightly increase anxiety, but not to a significant extent. Interestingly, it appears to reduce the likelihood of sleep disorders. Given these factors, radiotherapy could be a more favorable option than chemotherapy. Patients undergoing chemotherapy reported significant sleep disturbances characterized by increased nocturnal awakenings and restlessness ( 28 ). Adolescents undergoing chemotherapy experience disrupted or poor-quality sleep at least three times per week, significantly ( 29 ), which is associated with fatigue, decreased alertness, and decreased satisfaction with the previous night's sleep quality ( 30 ). Patients who report sleep disturbances during chemotherapy have gene polymorphisms in the genes encoding IL-6 and TNF ( 31 ), leading to increased cytokine levels. Moreover, the effects of chemotherapy on sleep disturbance, such as increased nocturnal awakenings, may result from increased cortisol, cytokines, and a physiological cascade of immune and inflammatory responses( 32 , 33 ). More studies need to measure changes in cytokine levels in sleep disorders, but what the obtained results showed was that sleep disorders were associated with increased anxiety in children, and in turn, anxiety alters inflammatory cytokines. Despite the conflicting results on sleep disorders in children with cancer, what the present results confirmed in the current study is the strong association between cancer and its types with sleep disorders. Notably, cancer often leads to mood changes, with anxiety being just one of them. These findings suggest that as anxiety increases, sleep disorders are more likely to develop. Both sleep disorders and anxiety are associated with increased inflammatory and cancer cytokines that disrupt treatment and favor carcinoma tissue. Interfering with this vicious cycle would be a suitable and much cheaper treatment option, starting with the prevention and treatment of sleep disorders. Besides, in order to increase the recovery rate, the available treatment options should be coordinated with sleep disorders to reduce the cytokine resistance of sleep disorders and the subsequent increase in anxiety. Limitations and Findings In addition to the link between childhood cancer and sleep disorders, this study highlights the need to pay attention to and monitor sleep in the treatment plan for children with cancer. This study encountered a limited number of children, which prevented us from conducting a proper statistical analysis of the types of cancer. Of course, there are conflicting and contradictory results regarding the prevalence of sleep disorders in different types of cancer, which we were unable to answer. Conclusion The present research shed light on the connection between cancer and sleep disorders, as well as sleep disorders and anxiety. Sleep, anxiety, and cancer are a cycle that reinforces each other, and treating sleep disorders can start to eliminate this cycle. We hope future studies show cytokines alterations by sleep disturbance to prove sleep therapeutic efficacy. Declarations Ethics approval and consent to participate All procedures performed in this systematic review involving human participants were under the ethical standards of the Institutional and National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study was conducted under the supervision of the Neurology Department of Arak University of Medical Sciences (ethic code: IR.ARAKMU.REC.1401.249). Consent for publication The present study included a Legally Authorized Representative (LAR) for children under 18. All parents were informed about the investigation's objectives and process and provided their informed consent. Availability of data and materials All the data generated or analyzed during this study will be available upon reasonable request. Competing interests The authors declare no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions H.T. the study design and protocol development; oversaw the clinical trial implementation; contributed to data interpretation and manuscript writing. M.T. and P.R managed participant recruitment and retention; performed statistical analysis; drafted sections of the results and discussion. A.L.K Conducted literature review and provided expertise in clinical methodology; assisted in data collection and quality assurance; contributed to manuscript revisions. M.M.S supervised the overall project and ensured compliance with ethical standards; reviewed and approved the final manuscript. Acknowledgment The authors would like to thank the Department of Pediatrics at Arak University of Medical Sciences for their assistance in this study and for their efforts in verifying the obtained results. References Goel P, Goel A. Exploring the Evolution of Sleep Patterns From Infancy to Adolescence. Cureus. 2024;16(7). Li M, Wang N, Dupre ME. Association between the self-reported duration and quality of sleep and cognitive function among middle-aged and older adults in China. Journal of Affective Disorders. 2022;304:20-7. Sen A, Tai XY. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7420057","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":511441354,"identity":"22306267-677d-4236-97be-ab4219339ed9","order_by":0,"name":"Atbin Latifi Kasani","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Atbin","middleName":"Latifi","lastName":"Kasani","suffix":""},{"id":511441355,"identity":"d2dbff28-8d92-4e59-a271-c9084565e6db","order_by":1,"name":"Mohaddese Mohammad Salehi","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohaddese","middleName":"Mohammad","lastName":"Salehi","suffix":""},{"id":511441356,"identity":"f6c477ab-9592-4e42-9d2e-b8141aa0654d","order_by":2,"name":"Majid Taheri","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Majid","middleName":"","lastName":"Taheri","suffix":""},{"id":511441357,"identity":"e4bd9097-f146-477c-8c2d-aa4f072d66d8","order_by":3,"name":"Parisa Rajabi","email":"","orcid":"","institution":"Arak University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Parisa","middleName":"","lastName":"Rajabi","suffix":""},{"id":511441358,"identity":"dec01ec2-7473-403b-819f-b33ab052cddb","order_by":4,"name":"Hassan Taherahmadi","email":"data:image/png;base64,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","orcid":"","institution":"Qazvin University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Taherahmadi","suffix":""}],"badges":[],"createdAt":"2025-08-20 18:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7420057/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7420057/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90929201,"identity":"29c9bf21-3eec-4897-b52e-8b1e9e576cbe","added_by":"auto","created_at":"2025-09-09 16:04:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":421115,"visible":true,"origin":"","legend":"\u003cp\u003einclusion and exclusion criteria for participant selection\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7420057/v1/665ce62ba450a0f65d713395.png"},{"id":90930641,"identity":"9cc314f8-8f50-49c6-95f1-4a658e61850d","added_by":"auto","created_at":"2025-09-09 16:12:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":915101,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7420057/v1/77fef122-7b5d-4109-bf1d-5d29865ec9ba.pdf"},{"id":90929204,"identity":"52760060-c661-4aa4-a286-eba6e8f897b9","added_by":"auto","created_at":"2025-09-09 16:04:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":30974,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7420057/v1/22dd66cfacfafdb8458739a9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe sleep-anxiety-cancer triad in pediatrics: Unraveling a vicious cycle \u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSleep disorders that postpone children\u0026rsquo;s growth process could change brain structure and reduce network efficacy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Improving brain functions and nerve pathways is linked to treatment opportunities focusing on sleep duration and quality, specifically in children. Prioritizing quality sleep in pediatrics is essential, as inadequate sleep duration and poor sleep quality can negatively affect cognitive and emotional functions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), as well as direct immunological pathways to control inflammation (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). As Interleukin-6(IL-6) and C reactive protein (CRP) increase in sleep disturbance (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), cancer-related cytokines and their signaling pathways, even radiotherapy efficacy, aliterate by sleep quality distraction (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Pioneering medicine should change its vision of sleep to a therapeutic procedure, particularly as therapeutic choices are at risk of anxiety and stress.\u003c/p\u003e\u003cp\u003eProinflammatory and tumor factors change through anxiety and stress that parallel the worst therapeutic results (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Anxiety reduces immunological potency (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) and increases levels of TNF-a and IL-6, which are key cytokines involved in the development of cancer (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). As a result, incorporating meditation and relaxation techniques into treatment plans is now considered an essential aspect of cancer therapy. Patients under chemo or radiotherapies usually show stress and anxiety by losing treatment effectiveness and rehabilitation ratio (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Whether children with normal sleep show lower anxiety levels (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), the ambiguity of sleep disturbance level correlation with anxiety levels is unclear. This investigation gathered children who suffered from cancer to terminate arguments about the correlation between sleep disturbance, anxiety, and cancer in children.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy oversight\u003c/h2\u003e\u003cp\u003e This study was conducted as a cross-sectional analysis at the Arak University of Science and Medical Sciences, Arak, Iran, with the approval of the Arak medical science university's ethics committee, to elucidate sleep disorders in children afflicted with cancer. Children referred to Amir Kabir Hospital who were experiencing sleep disorders were compared with control groups. Participants were recruited from children referred between September 2022 and March 2023, with parents responding to inquiries regarding sleep disorders. Informed consent was obtained in line with the Hilinski Declaration and the standards for Legally Authorized Representatives (LAR). This manuscript is structured according to the STROBE checklist.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipant\u003c/h3\u003e\n\u003cp\u003e A pediatric physician assessed children up to 15 years old diagnosed with cancer to assess sleep disorders based on the American Academy of Sleep Medicine (AASM) guideline specialized for pediatrics (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The diagnosis of cancer and its types were reviewed based on symptoms and final confirmation by a pediatric oncologist. Mothers were also assured that their children's details would remain confidential to the researchers.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA profile was created for each child, including demographic and sleep disorder test results, anxiety results, cancer type, and anthropometric data. The specialist physician assessed the anthropometry index for every patient, and the Children's Sleep Habits Questionnaire measured sleep disorders. Mothers answered the questions with the support of an impartial interviewer familiar with the questionnaire. Ultimately, the interviewer finalized a checklist that encompassed demographic and age-related details, such as the child's age in months, gender, birth order, aspirations of the child, the count of children under six years old, as well as the employment and educational background of the parents, household size, housing conditions regarding infrastructure quality, type of home ownership, ethnicity, and religious affiliation.\u003c/p\u003e\n\u003ch3\u003eChildren's Sleep Disorders Questionnaire (CSHQ)\u003c/h3\u003e\n\u003cp\u003eThe Children's Sleep Disorders Questionnaire (CSHQ) was used to measure children's sleep patterns over the past two weeks. It is designed for children 4 to 12 years of age and provides a broad description of children's sleep patterns. The CSHQ yields a total sleep disorder score and is measured for eight scales (resistance to sleep onset, sleep onset delay, sleep duration, sleep anxiety, nighttime awakenings, parasomnias, sleep-disordered breathing, and daytime sleepiness). Internal consistency measures for the entire scale are high (α\u0026thinsp;=\u0026thinsp;0.68 among a community sample, α\u0026thinsp;=\u0026thinsp;0.78 among a clinical sample), and test-retest reliability across scales is high (r\u0026thinsp;=\u0026thinsp;0.62 to 0.79). A CSHQ total score\u0026thinsp;\u0026ge;\u0026thinsp;41 has a sensitivity and specificity of 0.80 and 0.72, respectively, correctly classifying 80% of the population with clinically relevant sleep disorders. This questionnaire was completed under the supervision of an impartial interviewer knowledgeable about the questionnaire to ensure uniform and complete completion.\u003c/p\u003e\u003cp\u003eThis questionnaire consists of 33 multiple-choice items and provides information about nighttime sleep hours, wakefulness patterns, daytime sleepiness, and similar factors from the previous week. This questionnaire consisted of eight subscales as follows:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eBedtime resistance (items 1, 3, 4, 5, 6, 8)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSleep onset delay (item 2)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSleep duration (items 9, 10, 11)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSleep disturbance (items 5, 7, 8, 21)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNighttime awakenings (items 16, 24, 25)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eParasomnias (items 12, 13, 14, 15, 17, 22, 23)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eSleep-disordered breathing (items 18, 19, 20)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eDaytime sleepiness (items 26\u0026ndash;33).\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThe items are scored on a Likert scale (usually, sometimes, rarely) from 1 to 3. Thus, if the behavior is repeated 5\u0026ndash;7 days a week, the option is usually marked (score 3), 2\u0026ndash;4 times a week, the option is sometimes marked (score 2), and 0\u0026ndash;1 times a week, the option is rarely marked (score 1). Items 1-2-3-1011-26 are inverted. The scoring method of the tool is such that the higher the full score obtained from the tool, the more inappropriate the child's sleep situation is. The minimum and maximum scores of this questionnaire are 33 and 99.\u003c/p\u003e\n\u003ch3\u003eAnxiety scale\u003c/h3\u003e\n\u003cp\u003eThe Spence Child Anxiety Inventory (SCAS) was used to measure child anxiety. This scale is one of the most widely used tools in assessing anxiety symptom dimensions. The parent answering form of this scale had 38 items and was rated on a Likert scale from 0 (never) to 3 (always), with the highest score being 114. This scale assessed anxiety symptoms in six subtypes: Separation anxiety, social phobia/agoraphobia, generalized anxiety, specific phobia, fear of injury, and obsessive-compulsive disorder. This questionnaire has acceptable internal consistency (Cronbach's alpha 89%). The reliability and validity of the Japanese version of this scale have also been reported to be satisfactory.\u003c/p\u003e\n\u003ch3\u003eAnthropometric assessments\u003c/h3\u003e\n\u003cp\u003eInformation such as children's weight, height, head circumference, body mass index (BMI), and anthropometric data was obtained by a specialist physician using common indicators to determine children's nutritional status, including weight-for-height (wasting), height-for-age (nutritional stunting), and weight-for-age (underweight), by comparing them with standard tables from the World Health Organization and based on Z-Score.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe research data were entered into SPSS software version 18 for data analysis. Descriptive statistics characterized and presented the types of sleep disorders by frequency tables. The associations of the sleep disorders with the variables under consideration were evaluated using logistic regression analysis, independent t-test analysis, and a chi-square (χ\u0026sup2;) test.\u003c/p\u003e\u003cp\u003eA normality test was performed to evaluate the normality of the data. The data were analyzed based on the normality assessment results. For normally distributed data, independent t-tests were employed to compare the continuous variables in case and control groups. The Kolmogorov-Smirnov test confirmed the distribution of the data, thus aiding the selection of appropriate statistical methods. Categorical variables, such as demographic characteristics (gender, parental education, and environmental tobacco smoke exposure), as well as several sleep disorders, were subjected to chi-square (χ\u0026sup2;) tests for significant association. This study conducted logistic regression analyses to explore how various independent variables such as demographic factors, body measurements, and environmental exposure impact sleep disorders in children. These analyses accounted for potential confounding factors to ensure accurate results. All the statistical tests were carried out at significance level α\u0026thinsp;=\u0026thinsp;0.05 and power\u0026thinsp;=\u0026thinsp;80% β\u0026thinsp;=\u0026thinsp;0.20. Previous studies-derived odds ratio (OR) (2.14\u0026thinsp;=\u0026thinsp;OR) has been used for calculating sample size. Based on these, the required sample size was 212 participants (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipants\u003c/h2\u003e\n \u003cp\u003eThe present study assessed 212 children (age mean: 7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 years old) who suffered from leukemia, lymphoma, and malformation. ALL in leukemia and non-Hodgkin in lymphoma types had the most distribution. Less than 10% were in stage one or four, and 16.4% had a recurrence, and they were under surgery, radiotherapy, and chemotherapy (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eMore than half of mothers had a diploma or lower education level, compared to only 45.8% of fathers with bachelor\u0026apos;s degrees. Before pregnancy, 11.3% of mothers smoked, with only 1.4% smoking more than 10 cigarettes daily, and many reduced their smoking during breastfeeding. During this period, only 3.8% of mothers continued to smoke. Moreover, 23.5% of mothers were exposed to secondhand smoke from fathers, creating a passive smoking environment before pregnancy (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eThe total sleep score did not change significantly based on the anxiety score\u003c/h2\u003e\n \u003cp\u003eDependency of anxiety and total sleep disorders mark did not significantly, even though the studied children showed high levels in both of these variables. Daytime sleepiness and delayed sleep onset were both directly affected by anxiety scores, while resistance to going to bed, parasomnias, and sleep disturbance were inversely affected by anxiety scores (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Sleep disorders were directly related to the child\u0026apos;s height and inversely related to the child\u0026apos;s head circumference and the mother\u0026apos;s occupation. Anxiety was directly related to the child\u0026apos;s age and inversely related to the father\u0026apos;s education (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eSleep disturbances vary depending on the type of cancer\u003c/h2\u003e\n \u003cp\u003eCancer stages, surgery treatments, and cancer recurrence do not change total sleep disorders; however, cancer type and chemotherapy could directly change this mark level. Radiotherapy was inversely associated with the total sleep disturbance score, associated with the children\u0026apos;s overall sleep hygiene. Children who were undertreated by chemotherapy had lower anxiety marks, and this inverse ratio is also visible in recurrence (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe average of anxiety, sleep disorders, and its dimensions showed that the average total score of sleep disorders among these children was 26.55. The lowest rate of sleep disorders was 38%, and the highest rate was 82%. Furthermore, the lowest anxiety score was 58, and the highest rate was 100, indicating a high proportion of sleep disorders and anxiety among these children. The findings indicate a direct relationship between anxiety and delayed sleep onset, an inverse relationship with parasomnia, and a direct and significant relationship with daytime sleepiness. A positive correlation was found between sleep disorders and chemotherapy and the type of cancer. Additionally, a negative correlation was observed between anxiety, chemotherapy, and recurrence.\u003c/p\u003e\u003cp\u003eEach of the components of the disorder, such as pain, BMI, and physical activity limitations, may serve as a modifiable target for interventions to improve sleep quality in patients and survivors (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The impact on Hodgkin lymphoma (HL) survivors was similar to that in obese survivors of CNS tumors (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), with higher BMI scores associated with higher risks of sleep problems. This suggests that BMI is a predictive factor that influences sleep quality in lymphoma survivors and may be interpreted as a cause of sleep disturbance in other survivors (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), regardless of cancer type. Sleep disturbances were directly associated with child height and inversely associated with child head circumference, maternal occupation, and income (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The course of cancer and subsequent elective treatments are linked to changes in anthropometric indices, specifically in children, where these indices reflect growth status (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The obtained findings indicate that weight loss during cancer treatment is linked to higher rates of sleep and anxiety disorders(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDuring childhood leukemia treatment, the child's mood, coping skills, and self-soothing skills are affected by the cancer diagnosis (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), leading to increased psychological distress, which is crucial to examine, given that depression or clinical anxiety is reported in approximately one-quarter of pediatric cancer patients and survivors (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Insomnia is one of the most common sleep problems that have a strong bidirectional relationship with anxiety, a phenomenon that is also observed in childhood leukemia survivors(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Adult survivors of childhood cancer who suffer from insomnia often experience heightened anxiety. Depression in childhood cancer survivors leads to an increased prevalence of sleep problems, such as increased excessive daytime sleepiness (EDS). When analyzing the reciprocal effect of sleep and mood disorders, a vicious cycle emerges in which sleep disorders can be both a cause and a consequence of psychological distress.\u003c/p\u003e\u003cp\u003eMood, behavior, and the patient's and caregiver's inherent psychological predisposition play an essential role in sleep (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Therefore, addressing these interconnected and multifactorial causes is significant to breaking the sleep and mood disorders cycle. The conflicting data on sleep in leukemia survivors lack satisfactory explanations and highlight the need for further research to uncover fundamental changes in sleep. The obtained results clearly show that the type of cancer is associated with an overall score of sleep disorders, and chemotherapy is also associated with higher levels of sleep disorders. When choosing a treatment, it should be kept in mind that chemotherapy may increase sleep disorders and worsen treatment outcomes. On the other hand, chemotherapy is associated with a lower chance of anxiety, which may be a result of the familiarity of the patient community with chemotherapy and their adaptation to this type of treatment. Radiotherapy may slightly increase anxiety, but not to a significant extent. Interestingly, it appears to reduce the likelihood of sleep disorders. Given these factors, radiotherapy could be a more favorable option than chemotherapy. Patients undergoing chemotherapy reported significant sleep disturbances characterized by increased nocturnal awakenings and restlessness (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Adolescents undergoing chemotherapy experience disrupted or poor-quality sleep at least three times per week, significantly (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), which is associated with fatigue, decreased alertness, and decreased satisfaction with the previous night's sleep quality (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Patients who report sleep disturbances during chemotherapy have gene polymorphisms in the genes encoding IL-6 and TNF (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), leading to increased cytokine levels. Moreover, the effects of chemotherapy on sleep disturbance, such as increased nocturnal awakenings, may result from increased cortisol, cytokines, and a physiological cascade of immune and inflammatory responses(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). More studies need to measure changes in cytokine levels in sleep disorders, but what the obtained results showed was that sleep disorders were associated with increased anxiety in children, and in turn, anxiety alters inflammatory cytokines.\u003c/p\u003e\u003cp\u003eDespite the conflicting results on sleep disorders in children with cancer, what the present results confirmed in the current study is the strong association between cancer and its types with sleep disorders. Notably, cancer often leads to mood changes, with anxiety being just one of them. These findings suggest that as anxiety increases, sleep disorders are more likely to develop. Both sleep disorders and anxiety are associated with increased inflammatory and cancer cytokines that disrupt treatment and favor carcinoma tissue. Interfering with this vicious cycle would be a suitable and much cheaper treatment option, starting with the prevention and treatment of sleep disorders. Besides, in order to increase the recovery rate, the available treatment options should be coordinated with sleep disorders to reduce the cytokine resistance of sleep disorders and the subsequent increase in anxiety.\u003c/p\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eLimitations and Findings\u003c/h2\u003e\u003cp\u003eIn addition to the link between childhood cancer and sleep disorders, this study highlights the need to pay attention to and monitor sleep in the treatment plan for children with cancer.\u003c/p\u003e\u003cp\u003eThis study encountered a limited number of children, which prevented us from conducting a proper statistical analysis of the types of cancer. Of course, there are conflicting and contradictory results regarding the prevalence of sleep disorders in different types of cancer, which we were unable to answer.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present research shed light on the connection between cancer and sleep disorders, as well as sleep disorders and anxiety. Sleep, anxiety, and cancer are a cycle that reinforces each other, and treating sleep disorders can start to eliminate this cycle. We hope future studies show cytokines alterations by sleep disturbance to prove sleep therapeutic efficacy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in this systematic review involving human participants were under the ethical standards of the Institutional and National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study was conducted under the supervision of the Neurology Department of Arak University of Medical Sciences (ethic code:\u0026nbsp;IR.ARAKMU.REC.1401.249).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study included a Legally Authorized Representative (LAR) for children under 18. All parents were informed about the investigation\u0026apos;s objectives and process and provided their informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data generated or analyzed during this study will be available upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH.T. the study design and protocol development; oversaw the clinical trial implementation; contributed to data interpretation and manuscript writing. M.T. and P.R managed participant recruitment and retention; performed statistical analysis; drafted sections of the results and discussion. A.L.K Conducted literature review and provided expertise in clinical methodology; assisted in data collection and quality assurance; contributed to manuscript revisions. M.M.S supervised the overall project and ensured compliance with ethical standards; reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the Department of Pediatrics at Arak University of Medical Sciences for their assistance in this study and for their efforts in verifying the obtained results.\u003c/p\u003e "},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGoel P, Goel A. Exploring the Evolution of Sleep Patterns From Infancy to Adolescence. Cureus. 2024;16(7).\u003c/li\u003e\n\u003cli\u003eLi M, Wang N, Dupre ME. 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Sleep disturbance, obesity, physical fitness and quality of life in older women: EXERNET study group. Climacteric. 2017;20(1):72-9.\u003c/li\u003e\n\u003cli\u003eRogers LQ, Courneya KS, Oster RA, Anton PM, Robbs RS, Forero A, et al. Physical Activity and Sleep Quality in Breast Cancer Survivors: A Randomized Trial. Med Sci Sports Exerc. 2017;49(10):2009-15.\u003c/li\u003e\n\u003cli\u003eHammersen F, Lewin P, Gebauer J, Kreitschmann-Andermahr I, Brabant G, Katalinic A, et al. Sleep quality and health-related quality of life among long-term survivors of (non-) Hodgkin lymphoma in Germany. PLoS One. 2017;12(11):e0187673.\u003c/li\u003e\n\u003cli\u003eRach AM, Crabtree VM, Brinkman TM, Zeltzer L, Marchak JG, Srivastava D, et al. Predictors of fatigue and poor sleep in adult survivors of childhood Hodgkin\u0026rsquo;s lymphoma: a report from the Childhood Cancer Survivor Study. Journal of Cancer Survivorship. 2017;11(2):256-63.\u003c/li\u003e\n\u003cli\u003eSnell EK, Adam EK, Duncan GJ. 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Caregiver Emotion Socialization \u0026amp; Child Adjustment in Context of Pediatric Cancer 2025.\u003c/li\u003e\n\u003cli\u003eFerraz A, Santos M, Pereira MG. Parental distress in childhood acute lymphoblastic leukemia: A systematic review of the literature. Journal of Family Psychology. 2024;38(1):149.\u003c/li\u003e\n\u003cli\u003eStefanski KJ, Anixt JS, Goodman P, Bowers K, Leisenring W, Scott Baker K, et al. Long-term neurocognitive and psychosocial outcomes after acute myeloid leukemia: a childhood cancer survivor study report. JNCI: Journal of the National Cancer Institute. 2021;113(4):481-95.\u003c/li\u003e\n\u003cli\u003eSheikh IN, Roth M, Stavinoha PL. Prevalence of sleep disturbances in pediatric cancer patients and their diagnosis and management. Children. 2021;8(12):1100.\u003c/li\u003e\n\u003cli\u003eHoyt MA, Mazza MC, Ahmad Z, Darabos K, Applebaum AJ. Sleep quality in young adult informal caregivers: understanding psychological and biological processes. International Journal of Behavioral Medicine. 2021;28:6-13.\u003c/li\u003e\n\u003cli\u003eMukherjee U, Sehar U, Brownell M, Reddy PH. Mechanisms, consequences and role of interventions for sleep deprivation: Focus on mild cognitive impairment and Alzheimer\u0026rsquo;s disease in elderly. Ageing Research Reviews. 2024;100:102457.\u003c/li\u003e\n\u003cli\u003ePozzar RA, Hammer MJ, Paul SM, Cooper BA, Kober KM, Conley YP, et al. Distinct sleep disturbance profiles among patients with gynecologic cancer receiving chemotherapy. Gynecologic oncology. 2021;163(2):419-26.\u003c/li\u003e\n\u003cli\u003eKruszecka-Kr\u0026oacute;wka A, Cepuch G, Kr\u0026oacute;likowska A, Micek A, editors. Acceptance of Illness, Quality of Sleep and Emotional State of Adolescents with Lymphatic Malignancy During the First Cycle of Anticancer Treatment\u0026mdash;A Preliminary Report. Healthcare; 2025.\u003c/li\u003e\n\u003cli\u003eKudubes AA, Bektas M, Gerceker G\u0026Ouml;. The Predictive Power of Pain Characteristics and Sleep Quality on Fatigue in Adolescents With Cancer. Journal of Pediatric Hematology/Oncology. 2023;45(6):301-8.\u003c/li\u003e\n\u003cli\u003eHajj A, Chamoun R, Salameh P, Khoury R, Hachem R, Sacre H, et al. Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors. BMC cancer. 2022;22:1-11.\u003c/li\u003e\n\u003cli\u003eWhalen LB, Wright WZ, Kundur P, Angadi S, Modesitt SC. Beneficial effects of exercise on chemotherapy-induced peripheral neuropathy and sleep disturbance: A review of literature and proposed mechanisms. Gynecologic oncology reports. 2022;39:100927.\u003c/li\u003e\n\u003cli\u003eKarvandi R. Exploring Emotion Regulation and Social Support as Moderators of the Relationship between Sleep Disturbance and High Cortisol Levels in Cancer Survivors. 2023.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sleep-science-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssap","sideBox":"Learn more about [Sleep Science and Practice](http://sleep.biomedcentral.com)","snPcode":"41606","submissionUrl":"https://submission.nature.com/new-submission/41606/3","title":"Sleep Science and Practice","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sleep disorders, Anxiety, Cancer, Children, chemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-7420057/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7420057/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSleep disorders in children are associated with developmental and cognitive impairments, but their interaction with cancer has been unclear in previous studies. This cross-sectional study was conducted to investigate the association between sleep disorders in children with cancer and their impact on anxiety in these children.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe present study examined children with various types of cancer who were referred to Amir Kabir Hospital, Markazi Province, Iran, over a 6-month period, using the Spence Children's Anxiety Questionnaire (SCAS) and the Children's Sleep Disorders Questionnaire (CSHQ). Children underwent anthropometric examinations, and child weight, child height, child head circumference, body mass index, weight-for-height ratio (wasting), height-for-age ratio (nutritional short stature), and weight-for-age ratio (underweight) were statistically analyzed along with sleep and anxiety scores.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe mean total sleep disorder score among these children was 26.55, and the mean anxiety score among children was 34.74. A direct relationship was observed between anxiety and delayed sleep onset, an inverse relationship with parasomnia, and a direct and significant relationship with daytime sleepiness. A positive correlation was found between sleep disorders and cancer type and chemotherapy, and a negative correlation was observed between anxiety and chemotherapy and relapse.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSleep disturbance associated with cancer can increase anxiety, creating a cycle that may worsen cancer-related factors. This cycle can lead to lower treatment effectiveness in children. The obtained evidence suggests that managing sleep disorders may be a crucial first step in breaking this cycle.\u003c/p\u003e","manuscriptTitle":"The sleep-anxiety-cancer triad in pediatrics: Unraveling a vicious cycle","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 16:04:14","doi":"10.21203/rs.3.rs-7420057/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-16T17:16:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-14T17:35:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-13T06:27:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-10T09:55:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-03T22:23:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"298839193928041374690271404350852450529","date":"2025-09-03T21:40:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"263476258405039538767648548634182784117","date":"2025-09-03T10:50:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"89667919879341153845190419074809504175","date":"2025-09-03T08:03:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253052666440212140508428514644011115791","date":"2025-09-03T05:47:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-02T23:36:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-29T00:47:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-29T00:46:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Sleep Science and Practice","date":"2025-08-20T18:27:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sleep-science-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssap","sideBox":"Learn more about [Sleep Science and Practice](http://sleep.biomedcentral.com)","snPcode":"41606","submissionUrl":"https://submission.nature.com/new-submission/41606/3","title":"Sleep Science and Practice","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a4dc877-a33e-4608-9858-5548001a0a8a","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2025-12-23T14:24:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 16:04:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7420057","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7420057","identity":"rs-7420057","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}