{"paper_id":"17119a7c-022e-40d1-85a9-5eb8e82d7db3","body_text":"Diagnostic Delay in Children With Coeliac Disease: A national multicentre study in Turkey | 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 Diagnostic Delay in Children With Coeliac Disease: A national multicentre study in Turkey Yasin Sahin, Eylem Sevinc, Fatma Ilknur Varol, Ulas Emre Akbulut, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7133140/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jan, 2026 Read the published version in BMC Gastroenterology → Version 1 posted 16 You are reading this latest preprint version Abstract Objectives There is few studies conducted investigating diagnostic delay in children with celiac disease (CD). A better understanding of the factors associated with diagnostic delay and the development of strategies to reduce it are important in preventing long-term complications related to the disease. This study aimed to determine the average diagnostic delay in children with CD and to investigate possible underlying factors associated with diagnostic delay. Methods A prospective screening program was performed in children with CD at the seven clinical centers operating in Turkey within the Focus IN CD project between June 2021 and June 2023. Paediatric gastroenterologists were asked to complete a web-based questionnaire about CD. Results The median ages of the 188 celiac patients (66 male; 35%) were 8,33 (1,34 − 18,17) years. The median diagnostic delay was 7,3 months (0,03-133,9). Upon patient with CD were categorised according to OSLO criteria, The median delay for classic CD group, nonclassic CD group and silent CD group were found 14.31 (11.14–17.47), 11.98 (2.52–21.44) and 9.49 (3.48–15.49) month respectively. There were no significant differences between the patients with classic CD group and the nonclassic CD group and silent CD group (p = 1.000 and p = 0,939, respectively) Conclusions The study revealed that median diagnostic delay was 7,3 months. Furthermore there were no significant differences clinical subtypes of CD. In order to minimize the delay in diagnosis, it may be a solution to rise community-based awareness of CD and better informing pediatricians and family physicians about CD. celiac disease children diagnostic delay INTRODUCTION Celiac disease (CD), also known gluten-sensitive enteropathy, is triggered by the intake of gluten, mainly wheat, rye and barley in genetically susceptible individuals. Despite fact that the prevalence of CD varies depending on ethnic, geographical and even continental differences, Its prevalence is approximately 0.7–1.4% in various countries ( 1 ). Clinical presentation of CD in young children and adolescent is extremely variable. It can be clinically defined as classic, non-classic and asymptomatic (latent or potential form). Patients with classical CD have symptoms including chronic diarrhea, abdominal pain, poor weight gain vomiting and severe malnutrition. Extraintestinal manifestations of CD such as anemia, abnormal liver function, osteopenia, osteoporosis, and neuropathy are commonly seen in adolescent with nonclassical CD ( 2 , 3 ). Due to the vague and atypical presentation of CD symptoms, diagnosis may be delayed; cases with diagnostic delays of up to 13 years have been reported in the literature ( 4 – 8 ). Since CD has long been known to lead to malnutrition, anaemia, osteoporosis, infertility, and even an increased risk of certain types of cancer if left untreated, it is important to diagnose the disease early and start the gluten-free diet (GFD) as soon as possible. Therefore it is clear that delays in diagnosis of CD could pave the way for the occurrence of these complications ( 9 , 10 ). It has long been accepted that the only way to confirm a diagnosis of CD is to perform an intestinal biopsy. However, recently, non-biopsy serology-based diagnosis of CD has also become possible ( 11 ). Once diagnosed with CD, a lifelong GFD is currently considered the merely effective treatment ( 1 ). Based on the idea that a delay in the diagnosis of CD has adverse effects on clinical outcomes, few studies have recently conducted to determine the diagnostic delay of the disease. However, in globally, there is limited data on diagnostic delay in both pediatric and adult CD ( 12 ). As mentioned above, the limited number of studies has been conducted investigating diagnostic delay in patients with CD. In addition, no study has estimated diagnostic delay in children with CD in Turkey. First aim of this study was to identify the average diagnostic delay of children with CD. Second aim was to investigate possible underlying factors associated with diagnostic delay. To our knowledge, this is the first study reported diagnostic delay of children with CD in Turkey. METHODS This prospective study was carried out between June 2021 and June 2023 in 7 different regions of Turkey, as a part of the Focus IN CD project. Paediatric gastroenterologists were asked to complete a web-based questionnaire, providing anonymised medical records of children who were diagnosed with CD. The questionnaire was focused on the clinical picture, duration of symptoms and diagnostic methods used, prior to diagnosis. Medical records of children with CD were analysed, taking into account the first symptoms associated with CD, the duration between the first visit to the paediatric gastroenterologist and confirmation of the definitive diagnosis. In addition, to determine the effect of different clinical manifestations of CD on diagnostic delays, patients were divided into 3 groups according to the Oslo classification: classical CD and non-classical CD and no symptoms (high-risk group). The coeliac patients with comorbid disease were excluded. Statistical Analysis The data were analyzed with IBM SPSS statistic 21.0 for Windows. Results are expressed as median (range) or mean (SD). The Kolmogorov-Smirnov test was used to determine the normality of data distribution. Comparison of values between groups was made using Mann-Whitney U test and student t tests. One-way ANOVA test with post hoc tests were used for the analysis. Correlation analyses were evaluated with Spearman’s correlation test. A p value of less than 0.05 was considered to be statistically significant. Ethics Statement Written informed consent was obtained from the parents of all participants before the study. The study was approved by the Local Clinical Research Ethics Board (Sanko University, Gaziantep, Turkey, June 2, 2021/06). Also, the study was conducted in accordance with the ethical standards in the Declaration of Helsinki. RESULTS There were 188 children and adolescents with CD from 7 regions of Turkey; Southeastern Anatolia Region (33.0%), Eastern Anatolia Region (18.6%), Mediterranean Region (18.1%), Marmara Region (17.0%), Aegean Region (8.5%), and Black Sea (4.8%) (Table 1). Mean age of participants (122 female; 64.9%) was 8.83 (1.34-18.17) years. Mean age of the children with CD at diagnosis was 9.00 years (1.47–18.31 years). The median delay from onset of first symptoms to diagnosis was 7.30 months (0,23–133,9) with no significant differences between regions (Table 2). There was no significant difference between patients with classical CD symptoms, non-classical CD symptoms and no symptoms (high risk-group patients) (Table 3). Among the 188 patients included in the study, 172 (91.5%) were diagnosed within the first three years, whereas 16 (8.5%) were diagnosed after three years. An evaluation of the presenting symptoms of the 16 patients diagnosed after three years revealed failure to thrive in 10 patients, constipation in 3, chronic abdominal pain in 2, and diarrhea in 1 patient. It was determined that patients with classical CD symptoms were diagnosed at a later stage. In Spearman rank correlation test, There was no correlation between age at diagnosis and diagnostic delays (r=- 0,68, P = 0.353). In 65,4% (123) of children, diagnostic delay was less than 1 year and in 16% (30) it was between 1 and 2 years. In 18,6% (35) of children, diagnostic delay exceeded 3 years and more. We found there is no correlation between diagnostic delays and BMI (r=,-011 P = 0.885 ). In addition, there is no statistically significant difference between diagnostic delays and anemia status (χ2: 4,232 - p: 0,121 for hb and χ2 :2,913 - p: 0,0233 for ferritin) After children with CD were categorised according to Oslo criteria, the mean delay time for classic CD group, nonclassic CD group and silent CD group were found 14.32 months (0.23-133.90), 12.00 months (0.40‐67.36) and 9.49 months (0.36‐ 35.60), respectively. There were no significant differences between the children with classic CD group, nonclassic CD group and silent CD group (p = 0.564). DISCUSSION The clinical presentation of CD has evolved over time, with classic symptoms such as abdominal distension, anorexia, chronic diarrhea, weight loss, and growth retardation becoming less prevalent in recent years (13,14). The increased presence of atypical and subtle findings leads to delays in diagnosis ( 15 ). Early diagnosis of CD and initiation of the GFD diet is very important to prevent long-term complications such as malnutrition, anaemia, osteoporosis, infertility, and intestinal lymphoma, small bowel adenocarcinoma. In the current study, we detected that the median delay from onset of first symptoms to diagnosis was 7.30 months (0,23–133,9). There is a limited study about diagnostic delay in children with CD. In a 2022 study involving children over the age of 12 and adults, patients were divided into two groups based on the time to diagnosis: those diagnosed within three years were classified as the early diagnosis group, while those diagnosed after more than three years were considered the delayed diagnosis group ( 16 ). Of the 570 patients included, 289 were in the early diagnosis group and 281 (49.3%) in the delayed diagnosis group. However, atypical symptoms were more prevalent in the delayed diagnosis group, with fewer complaints of diarrhea and higher rates of anemia, delayed puberty, and low vitamin D levels. Additionally, this group exhibited significantly higher tissue transglutaminase antibody (tTG) levels and more severe degrees of villous atrophy. In contrast to that study,16 of 188 patients (8.5%) were diagnosed more than 3 years later, and 68.7% of these patients had classical CD symptoms in our study. In addition to that, 6 of 16 (37.5%) had anemia. No assessment of vitamin D levels had been performed in the current study. A study similar to our study conducted across five countries in the Central European Region reported that the median diagnostic delay was detected 6 months (range 0 to 10 years) ( 12 ). However, diagnostic delay was observed to exceed three years in 6.6% of cases. The median age at diagnosis was 9 years, with 73.1% of the patients being female. This study also found that patients presenting with non-classical symptoms were referred to pediatric gastroenterologists later, and statistically exhibited a longer diagnostic delay. Conversely, patients with classical CD symptoms experienced a shorter time to diagnosis. Notably, a shorter diagnostic interval was reported particularly in symptomatic patients. Differences between regions were attributed to variations in diagnostic methods used and the capacity of pediatric gastroenterology specialists. Additionally, a prolonged diagnostic delay was particularly noted in seven patients diagnosed with dermatitis herpetiformis. In this study, among the limited number of patients with dermatitis herpetiformis, the median diagnostic delay was 8 months (ranging from 1 month to 1.5 years). Parallel to this study, the median age of participants (122 female; 64.9%) was 8.49, the median delay from onset of first symptoms to diagnosis was 7.30 months (range 0.23-133.9 months), and 16 of 188 patients (8.5%) were diagnosed more than 3 years later, in our study. No significant differences between regions was found in terms of diagnostic delay. Conversely, patients with classical CD symptoms were diagnosed later in the current study. There were no patients with dermatitis herpetiformis in our study In a cohort study conducted in Finland involving adult patients, it was reported that 261 (31.6%) out of 825 individuals were diagnosed with CD more than ten years after symptom onset, indicating a considerable diagnostic delay ( 17 ). This prolonged delay was significantly correlated with female sex, neurological comorbidities, presence of diarrhea, abdominal pain, and malabsorption. Contrarily, no statistically significant difference was observed between diagnostic delay and clinical features such as weight loss, abdominal distension, or constipation. These findings highlight specific factors contributing to delayed diagnosis while challenging the conventional assumption that classic symptoms like weight loss and abdominal distension invariably predict diagnostic latency. In consistent with this study, there was no statistically significant difference between diagnostic delay and clinical features of CD in the present study, and also the majority of patients who experienced delayed diagnosis presented with classical symptoms of CD. In a web-based survey study conducted in Denmark involving adults, diagnostic delay was found to exceed 10 years in 18.6% of the 1,392 participants ( 18 ). The participants ranged in age from 3 to 87 years, with a median age of 42.7 years. In this study, 38% of the patients experienced a diagnostic delay exceeding 3 years. However, among patients under 18 years of age, 25% had a diagnostic delay longer than 3 years. In contrast, 16 out of 188 patients (8.5%) were diagnosed after more than 3 years. This discrepancy may be attributed to the presence of pediatric gastroenterologists in all participating centers in our study. A recent study conducted in India, including 726 adult patients, reported that the median interval from symptom onset to definitive diagnosis was 27 months (ranging from 12 to 60 months) ( 19 ). Delayed diagnosis was found to be associated with short stature, low hemoglobin levels, elevated tTG antibody titers, and severe villous atrophy. It was reported that 18% of patients presenting with non-GI symptoms experienced a later diagnosis. The median time to diagnosis was 24 months (range 12–60 months) for those with GI symptoms, whereas for patients with non-GI symptoms, the median diagnostic interval extended to 48 months (range 24–96 months). Diagnosis was established more than 5 years after symptom onset in 24.2% of the patients. Among those diagnosed before 2016, the median delay was 36 months (range 12–72 months), whereas for patients diagnosed after 2022, the median delay decreased to 24 months (range 12–48 months). This decrease may be attributed to the increased awareness of CD and the widespread implementation of disease-specific serological testing in recent years In a study involving 1,138 adult patients in the United States, the average diagnostic delay for CD was reported to be 11 years, with diarrhea being the presenting symptom in 85% of cases ( 4 ). Similarly, Zipser et al. found that more than 21% of adult patients experienced a diagnostic delay exceeding 10 years ( 20 ). Consistent with these studies, classical symptoms of CD were observed in most patients who experienced diagnostic delays in our study, although the median duration of delay was only 7.3 months. In an another study conducted in the United States involving 101 biopsy-confirmed adult CD patients, the median diagnostic delay was reported as 2.3 months in individuals presenting with gastrointestinal symptoms, whereas those with non-gastrointestinal symptoms experienced a median delay of 42 months ( 8 ). Anemia was reported in 69.4% of patients with non-gastrointestinal symptoms, compared to 11.5% in those presenting with gastrointestinal symptoms. In this study, the notably shorter diagnostic delay observed in 52 cases with gastrointestinal symptoms compared to our findings may be attributed to the relatively small sample size. Conversely, our findings revealed a median diagnostic delay of 7.63 months in patients exhibiting gastrointestinal symptoms, compared to 4.40 months in those with non-gastrointestinal manifestations. In contrast to that findings, a large multicenter study conducted in Italy involving 2,362 adult patients reported a median diagnostic delay of only 8 months ( 21 ). In this study, it was reported that 398 (17.5%) celiac patients were misdiagnosed at least once before receiving a definitive diagnosis. The most common misdiagnosis is irritable bowel syndrome. Since our study was prospective, there were no patients with misdiagnosis. But the median diagnostic delay time is similar to that study. The current study has some limitations. First; there is a small number of centers. Secondly, there is a small number of patients participated in the study. The strength of the current study is that it is a prospective study and centers from different regions from our country participated in the study. Due to that, we think this may reflect our country's data. CONCLUSIONS We detected that the median delay from onset of first symptoms to diagnosis was 7.30 months. It is promising that the delay in diagnosis is relatively low compared to the literature. Since CD has serious long-term complications, we aim to diagnose it even earlier in future. Diagnostic delays in CD significantly and adversely impact patients' quality of life and overall health. Consequently, diagnostic delay represents a public health concern. One of the primary reasons for diagnostic delay may be the limited awareness of CD among healthcare professionals. Therefore, increasing awareness through online seminars, dissemination of public service announcements, and implementation of comparable educational initiatives are essential. Additionally, screening for CD in high-risk groups can help reduce diagnostic delays. Abbreviations CD celiac disease GFD gluten-free diet tTG tissue transglutaminase antibody Declarations Ethics approval and consent to participate: Written informed consent was obtained from both the children and their parents (all parents of participing children who were under 16). The study was approved by the Local Clinical Research Ethics Board (Sanko University, Gaziantep, Turkey, June 2, 2021/06). Also, the study was conducted in accordance with the ethical standards in the Declaration of Helsinki. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare no competing interests. Fundings: None Authors contributions: Sahin Y, designed the study, collected the data, analyzed the data, interpreted the data, conception, and statistical analysis, and wrote the manuscript; Sevinc E, collected the data, analyzed the data, interpreted the data, and statistical analysis, and wrote the manuscript; Bayrak NA, Varol FI, Akbulut UA, and Bukulmez A collected the data, and analyzed the data; All authors had read and approved the final manuscript. Acknowledgements: We thank Kadriye Nil Bezci, MD for performing endoscopy on some patients in Gaziantep. References Sahin Y. Celiac disease in children: A review of the literature. World J Clin Pediatr 2021; 10: 53-71. Tarar ZI, Zafar MU, Farooq U, Basar O, Tahan V, Daglilar E. The progression of celiac disease, diagnostic modalities, and treatment options. J Investig Med High Impact Case Rep. 2021; 9: 23247096211053702. Crehuá-Gaudiza E, Barrés Fernández A, Jovaní Casano C, Latorre Tejerina M, Largo Blanco EM, Moreno Ruiz MA, et al. Diagnosis of celiac disease in clinical practice: Present and future. An Pediatr (Engl Ed). 2021; 94: 223-229. Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol. 2001; 96: 126-31. West J, Logan RF, Hill PG, Lloyd A, Lewis S, Hubbard R, et al. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut. 2003; 52: 960-5. Gray AM, Papanicolas IN. Impact of symptoms on quality of life before and after diagnosis of coeliac disease: results from a UK population survey. BMC Health Serv Res 2010; 10: 1-7. Norström F, Lindholm L, Sandström O, Nordyke K, Ivarsson A. Delay to celiac disease diagnosis and its implications for health-related quality of life. BMC Gastroenterol 2011; 11: 1-8. Paez MA, Gramelspacher AM, Sinacore J, Winterfield L, Venu M. Delay in diagnosis of celiac disease in patients without gastrointestinal complaints. Am J Med 2017; 130: 1318-23. Cosnes J, Nion-Larmurier I. Complications of celiac disease. Pathol Biol (Paris) 2013; 61: e21-6. Ivanova M, Bottiglieri L, Sajjadi E, Venetis K, Fusco N. Malignancies in patients with celiac disease: Diagnostic challenges and molecular advances. Genes (Basel). 2023 Jan 31; 14: 376. Ylönen V, Lindfors K, Repo M, Huhtala H, Fuchs V, Saavalainen P, et al. Non-biopsy serology-based diagnosis of celiac disease in adults is accurrate with different comercial kits and pre-test probabilities. Nutrients 2020; 12: 2736. Riznik P, De Leo L, Dolinsek J, Gyimesi J, Klemenak M, Koletzko B, et al. Diagnostic delay in children with coeliac disease in the Central European Region. J Pediatr Gastroenterol Nutr. 2019; 69: 443-448. Kho A, Whitehead M, Day AS. Coeliac disease in children in Christchurch, New Zealand: Presentation and patterns from 2000–2010. World J Clin Pediatr. 2015; 4: 148–54. Van Kalleveen MW, de Meij T, Plotz FB. Clinical spectrum of paediatric coeliac disease: a 10-year single-centre experience. Eur J Pediatr. 2018; 177: 593-602. Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001; 120: 636-51. Dhar J, Samanta J, Sharma M, Kumar S, Sinha SK, Kochar R. Impact of delay in diagnosis in patients with celiac disease: A study of 570 patients at a tertiary care center. Indian J Gasstroenterol 2022; 41: 30-36. Fuchs V, Kurppa K, Huhtala H, Collin P, Mäki M, Kaukinen K. Factors associated with long diagnostic delay in celiac disease. Scand J Gastroenterol. 2014; 49: 1304-10. Kårhus LL, Hansen S, Rumessen JJ, Linneberg A. Diagnostic Delay in Coeliac Disease: A Survey among Danish Patients. Can J Gastroenterol Hepatol 2022; 2022: 5997624. Mehta S, Agarwal A, Pachisia AV, Singh A, Dang S, Vignesh D, et al. Impact of delay in the diagnosis on the severity of celiac disease. J Gastroenterol Hepatol. 2024; 39: 256-263. Zipser RD, Patel S, Yahya KZ et al. Presentations of adult celiac disease in a nationwide patient support group. Dig Dis Sci 2003; 48: 761-4. Lenti MV, Aronico N, Bianchi PI et al. Diagnostic delay in adult coeliac disease: an Italian multicentre study. Dig Liver Dis 2023; 55: 743–50. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.docx Cite Share Download PDF Status: Published Journal Publication published 22 Jan, 2026 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 05 Sep, 2025 Reviews received at journal 01 Sep, 2025 Reviewers agreed at journal 01 Sep, 2025 Reviewers agreed at journal 27 Aug, 2025 Reviewers agreed at journal 26 Aug, 2025 Reviewers agreed at journal 26 Aug, 2025 Reviews received at journal 25 Aug, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviewers agreed at journal 06 Aug, 2025 Reviewers invited by journal 06 Aug, 2025 Editor assigned by journal 06 Aug, 2025 Editor invited by journal 01 Aug, 2025 Submission checks completed at journal 01 Aug, 2025 First submitted to journal 01 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7133140\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":499042238,\"identity\":\"e77d676d-8a71-4469-8d85-42e12d5abca6\",\"order_by\":0,\"name\":\"Yasin Sahin\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYHACNoYEBpv6/ccbgGwDC6K1pDE2nDkA0iJBpBYGhsOMDTcSQBwitBicP/zswcMdh5kZZz6/uuFHgQQDf3t3An4tN9LMDRLPpLMxS+eU3ewBOkzizNkNBLQwmEkktlnzsEnnpN3gAWoxkMgloOX88W9ALcwSPJJn0m7+IUrLgRyQLc4GEhLsx24TZYvkjZwyoJa0BAOeHLbbMgYSPAT9wnf++DbJn202CQbsx5/dfPPHRo6/vRe/FoUDcCaPAZjEqxwE5BvgTPYHBFWPglEwCkbByAQACJ1JAuH0KmkAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Dr. Ersin Arslan Training and Research Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Yasin\",\"middleName\":\"\",\"lastName\":\"Sahin\",\"suffix\":\"\"},{\"id\":499042240,\"identity\":\"c4ff974f-9437-499e-b6e6-f02c04b92390\",\"order_by\":1,\"name\":\"Eylem Sevinc\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Karabuk University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Eylem\",\"middleName\":\"\",\"lastName\":\"Sevinc\",\"suffix\":\"\"},{\"id\":499042243,\"identity\":\"46d62bf5-5f65-4b04-9480-a218bc657fda\",\"order_by\":2,\"name\":\"Fatma Ilknur Varol\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Inonu University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Fatma\",\"middleName\":\"Ilknur\",\"lastName\":\"Varol\",\"suffix\":\"\"},{\"id\":499042245,\"identity\":\"519ca1a5-b088-4e8b-913e-b3d396297849\",\"order_by\":3,\"name\":\"Ulas Emre Akbulut\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Health Sciences, Antalya Training and Research Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ulas\",\"middleName\":\"Emre\",\"lastName\":\"Akbulut\",\"suffix\":\"\"},{\"id\":499042247,\"identity\":\"846dc9a3-80ea-4dbd-b288-c47f9e905fea\",\"order_by\":4,\"name\":\"Nevzat Aykut Bayrak\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Health Sciences, Zeynep Kamil Women and Children's Training and Research Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nevzat\",\"middleName\":\"Aykut\",\"lastName\":\"Bayrak\",\"suffix\":\"\"},{\"id\":499042248,\"identity\":\"981846db-20e2-4264-ae6a-8805d10dbda0\",\"order_by\":5,\"name\":\"Aysegul Bukulmez\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Afyonkarahisar Health Sciences University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Aysegul\",\"middleName\":\"\",\"lastName\":\"Bukulmez\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-07-15 17:53:12\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-7133140/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7133140/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12876-026-04639-2\",\"type\":\"published\",\"date\":\"2026-01-22T15:58:31+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":101152484,\"identity\":\"5aeeda08-505a-4605-8ae4-813c4eb732e0\",\"added_by\":\"auto\",\"created_at\":\"2026-01-26 16:11:57\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":408752,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7133140/v1/0d3a52d4-96be-4d51-8255-242d27105e90.pdf\"},{\"id\":88878994,\"identity\":\"51a3d20b-61ff-4922-8e27-6ecf64d96131\",\"added_by\":\"auto\",\"created_at\":\"2025-08-12 10:42:58\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":15301,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Table.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7133140/v1/2300db417fd162a4594528fe.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Diagnostic Delay in Children With Coeliac Disease: A national multicentre study in Turkey\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003eCeliac disease (CD), also known gluten-sensitive enteropathy, is triggered by the intake of gluten, mainly wheat, rye and barley in genetically susceptible individuals. Despite fact that the prevalence of CD varies depending on ethnic, geographical and even continental differences, Its prevalence is approximately 0.7\\u0026ndash;1.4% in various countries (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Clinical presentation of CD in young children and adolescent is extremely variable. It can be clinically defined as classic, non-classic and asymptomatic (latent or potential form). Patients with classical CD have symptoms including chronic diarrhea, abdominal pain, poor weight gain vomiting and severe malnutrition. Extraintestinal manifestations of CD such as anemia, abnormal liver function, osteopenia, osteoporosis, and neuropathy are commonly seen in adolescent with nonclassical CD (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Due to the vague and atypical presentation of CD symptoms, diagnosis may be delayed; cases with diagnostic delays of up to 13 years have been reported in the literature (\\u003cspan additionalcitationids=\\\"CR5 CR6 CR7\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eSince CD has long been known to lead to malnutrition, anaemia, osteoporosis, infertility, and even an increased risk of certain types of cancer if left untreated, it is important to diagnose the disease early and start the gluten-free diet (GFD) as soon as possible. Therefore it is clear that delays in diagnosis of CD could pave the way for the occurrence of these complications (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eIt has long been accepted that the only way to confirm a diagnosis of CD is to perform an intestinal biopsy. However, recently, non-biopsy serology-based diagnosis of CD has also become possible (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). Once diagnosed with CD, a lifelong GFD is currently considered the merely effective treatment (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Based on the idea that a delay in the diagnosis of CD has adverse effects on clinical outcomes, few studies have recently conducted to determine the diagnostic delay of the disease. However, in globally, there is limited data on diagnostic delay in both pediatric and adult CD (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAs mentioned above, the limited number of studies has been conducted investigating diagnostic delay in patients with CD. In addition, no study has estimated diagnostic delay in children with CD in Turkey. First aim of this study was to identify the average diagnostic delay of children with CD. Second aim was to investigate possible underlying factors associated with diagnostic delay. To our knowledge, this is the first study reported diagnostic delay of children with CD in Turkey.\\u003c/p\\u003e\"},{\"header\":\"METHODS\",\"content\":\"\\u003cp\\u003eThis prospective study was carried out between June 2021 and June 2023 in 7 different regions of Turkey, as a part of the Focus IN CD project. Paediatric gastroenterologists were asked to complete a web-based questionnaire, providing anonymised medical records of children who were diagnosed with CD. The questionnaire was focused on the clinical picture, duration of symptoms and diagnostic methods used, prior to diagnosis. Medical records of children with CD were analysed, taking into account the first symptoms associated with CD, the duration between the first visit to the paediatric gastroenterologist and confirmation of the definitive diagnosis. In addition, to determine the effect of different clinical manifestations of CD on diagnostic delays, patients were divided into 3 groups according to the Oslo classification: classical CD and non-classical CD and no symptoms (high-risk group). The coeliac patients with comorbid disease were excluded.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec2\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e\\u003cp\\u003eThe data were analyzed with IBM SPSS statistic 21.0 for Windows. Results are expressed as median (range) or mean (SD). The Kolmogorov-Smirnov test was used to determine the normality of data distribution. Comparison of values between groups was made using Mann-Whitney U test and student t tests. One-way ANOVA test with post hoc tests were used for the analysis. Correlation analyses were evaluated with Spearman\\u0026rsquo;s correlation test. A p value of less than 0.05 was considered to be statistically significant.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eEthics Statement\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e Written informed consent was obtained from the parents of all participants before the study. The study was approved by the Local Clinical Research Ethics Board (Sanko University, Gaziantep, Turkey, June 2, 2021/06). Also, the study was conducted in accordance with the ethical standards in the Declaration of Helsinki.\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cp\\u003eThere were 188 children and adolescents with CD from 7 regions of Turkey; Southeastern Anatolia Region (33.0%), Eastern Anatolia Region (18.6%), Mediterranean Region (18.1%), Marmara Region (17.0%), Aegean Region (8.5%), and Black Sea (4.8%) (Table\\u0026nbsp;1). Mean age of participants (122 female; 64.9%) was 8.83 (1.34-18.17) years. Mean age of the children with CD at diagnosis was 9.00 years (1.47\\u0026ndash;18.31 years).\\u003c/p\\u003e\\u003cp\\u003eThe median delay from onset of first symptoms to diagnosis was 7.30 months (0,23\\u0026ndash;133,9) with no significant differences between regions (Table\\u0026nbsp;2). There was no significant difference between patients with classical CD symptoms, non-classical CD symptoms and no symptoms (high risk-group patients) (Table\\u0026nbsp;3).\\u003c/p\\u003e\\u003cp\\u003eAmong the 188 patients included in the study, 172 (91.5%) were diagnosed within the first three years, whereas 16 (8.5%) were diagnosed after three years. An evaluation of the presenting symptoms of the 16 patients diagnosed after three years revealed failure to thrive in 10 patients, constipation in 3, chronic abdominal pain in 2, and diarrhea in 1 patient. It was determined that patients with classical CD symptoms were diagnosed at a later stage.\\u003c/p\\u003e\\u003cp\\u003eIn Spearman rank correlation test, There was no correlation between age at diagnosis and diagnostic delays (r=- 0,68, P\\u0026thinsp;=\\u0026thinsp;0.353). In 65,4% (123) of children, diagnostic delay was less than 1 year and in 16% (30) it was between 1 and 2 years. In 18,6% (35) of children, diagnostic delay exceeded 3 years and more. We found there is no correlation between diagnostic delays and BMI (r=,-011 P\\u0026thinsp;=\\u0026thinsp;0.885 ). In addition, there is no statistically significant difference between diagnostic delays and anemia status (χ2: 4,232 - p: 0,121 for hb and χ2 :2,913 - p: 0,0233 for ferritin)\\u003c/p\\u003e\\u003cp\\u003eAfter children with CD were categorised according to Oslo criteria, the mean delay time for classic CD group, nonclassic CD group and silent CD group were found 14.32 months (0.23-133.90), 12.00 months (0.40‐67.36) and 9.49 months (0.36‐ 35.60), respectively. There were no significant differences between the children with classic CD group, nonclassic CD group and silent CD group (p\\u0026thinsp;=\\u0026thinsp;0.564).\\u003c/p\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eThe clinical presentation of CD has evolved over time, with classic symptoms such as abdominal distension, anorexia, chronic diarrhea, weight loss, and growth retardation becoming less prevalent in recent years (13,14). The increased presence of atypical and subtle findings leads to delays in diagnosis (\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). Early diagnosis of CD and initiation of the GFD diet is very important to prevent long-term complications such as malnutrition, anaemia, osteoporosis, infertility, and intestinal lymphoma, small bowel adenocarcinoma.\\u003c/p\\u003e\\u003cp\\u003eIn the current study, we detected that the median delay from onset of first symptoms to diagnosis was 7.30 months (0,23\\u0026ndash;133,9). There is a limited study about diagnostic delay in children with CD. In a 2022 study involving children over the age of 12 and adults, patients were divided into two groups based on the time to diagnosis: those diagnosed within three years were classified as the early diagnosis group, while those diagnosed after more than three years were considered the delayed diagnosis group (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e). Of the 570 patients included, 289 were in the early diagnosis group and 281 (49.3%) in the delayed diagnosis group. However, atypical symptoms were more prevalent in the delayed diagnosis group, with fewer complaints of diarrhea and higher rates of anemia, delayed puberty, and low vitamin D levels. Additionally, this group exhibited significantly higher tissue transglutaminase antibody (tTG) levels and more severe degrees of villous atrophy. In contrast to that study,16 of 188 patients (8.5%) were diagnosed more than 3 years later, and 68.7% of these patients had classical CD symptoms in our study. In addition to that, 6 of 16 (37.5%) had anemia. No assessment of vitamin D levels had been performed in the current study.\\u003c/p\\u003e\\u003cp\\u003eA study similar to our study conducted across five countries in the Central European Region reported that the median diagnostic delay was detected 6 months (range 0 to 10 years) (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). However, diagnostic delay was observed to exceed three years in 6.6% of cases. The median age at diagnosis was 9 years, with 73.1% of the patients being female. This study also found that patients presenting with non-classical symptoms were referred to pediatric gastroenterologists later, and statistically exhibited a longer diagnostic delay. Conversely, patients with classical CD symptoms experienced a shorter time to diagnosis. Notably, a shorter diagnostic interval was reported particularly in symptomatic patients. Differences between regions were attributed to variations in diagnostic methods used and the capacity of pediatric gastroenterology specialists. Additionally, a prolonged diagnostic delay was particularly noted in seven patients diagnosed with dermatitis herpetiformis. In this study, among the limited number of patients with dermatitis herpetiformis, the median diagnostic delay was 8 months (ranging from 1 month to 1.5 years). Parallel to this study, the median age of participants (122 female; 64.9%) was 8.49, the median delay from onset of first symptoms to diagnosis was 7.30 months (range 0.23-133.9 months), and 16 of 188 patients (8.5%) were diagnosed more than 3 years later, in our study. No significant differences between regions was found in terms of diagnostic delay. Conversely, patients with classical CD symptoms were diagnosed later in the current study. There were no patients with dermatitis herpetiformis in our study\\u003c/p\\u003e\\u003cp\\u003eIn a cohort study conducted in Finland involving adult patients, it was reported that 261 (31.6%) out of 825 individuals were diagnosed with CD more than ten years after symptom onset, indicating a considerable diagnostic delay (\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e). This prolonged delay was significantly correlated with female sex, neurological comorbidities, presence of diarrhea, abdominal pain, and malabsorption. Contrarily, no statistically significant difference was observed between diagnostic delay and clinical features such as weight loss, abdominal distension, or constipation. These findings highlight specific factors contributing to delayed diagnosis while challenging the conventional assumption that classic symptoms like weight loss and abdominal distension invariably predict diagnostic latency. In consistent with this study, there was no statistically significant difference between diagnostic delay and clinical features of CD in the present study, and also the majority of patients who experienced delayed diagnosis presented with classical symptoms of CD.\\u003c/p\\u003e\\u003cp\\u003eIn a web-based survey study conducted in Denmark involving adults, diagnostic delay was found to exceed 10 years in 18.6% of the 1,392 participants (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e). The participants ranged in age from 3 to 87 years, with a median age of 42.7 years. In this study, 38% of the patients experienced a diagnostic delay exceeding 3 years. However, among patients under 18 years of age, 25% had a diagnostic delay longer than 3 years. In contrast, 16 out of 188 patients (8.5%) were diagnosed after more than 3 years. This discrepancy may be attributed to the presence of pediatric gastroenterologists in all participating centers in our study.\\u003c/p\\u003e\\u003cp\\u003eA recent study conducted in India, including 726 adult patients, reported that the median interval from symptom onset to definitive diagnosis was 27 months (ranging from 12 to 60 months) (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e). Delayed diagnosis was found to be associated with short stature, low hemoglobin levels, elevated tTG antibody titers, and severe villous atrophy. It was reported that 18% of patients presenting with non-GI symptoms experienced a later diagnosis. The median time to diagnosis was 24 months (range 12\\u0026ndash;60 months) for those with GI symptoms, whereas for patients with non-GI symptoms, the median diagnostic interval extended to 48 months (range 24\\u0026ndash;96 months). Diagnosis was established more than 5 years after symptom onset in 24.2% of the patients. Among those diagnosed before 2016, the median delay was 36 months (range 12\\u0026ndash;72 months), whereas for patients diagnosed after 2022, the median delay decreased to 24 months (range 12\\u0026ndash;48 months). This decrease may be attributed to the increased awareness of CD and the widespread implementation of disease-specific serological testing in recent years\\u003c/p\\u003e\\u003cp\\u003eIn a study involving 1,138 adult patients in the United States, the average diagnostic delay for CD was reported to be 11 years, with diarrhea being the presenting symptom in 85% of cases (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e). Similarly, Zipser et al. found that more than 21% of adult patients experienced a diagnostic delay exceeding 10 years (\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e). Consistent with these studies, classical symptoms of CD were observed in most patients who experienced diagnostic delays in our study, although the median duration of delay was only 7.3 months.\\u003c/p\\u003e\\u003cp\\u003eIn an another study conducted in the United States involving 101 biopsy-confirmed adult CD patients, the median diagnostic delay was reported as 2.3 months in individuals presenting with gastrointestinal symptoms, whereas those with non-gastrointestinal symptoms experienced a median delay of 42 months (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). Anemia was reported in 69.4% of patients with non-gastrointestinal symptoms, compared to 11.5% in those presenting with gastrointestinal symptoms. In this study, the notably shorter diagnostic delay observed in 52 cases with gastrointestinal symptoms compared to our findings may be attributed to the relatively small sample size. Conversely, our findings revealed a median diagnostic delay of 7.63 months in patients exhibiting gastrointestinal symptoms, compared to 4.40 months in those with non-gastrointestinal manifestations.\\u003c/p\\u003e\\u003cp\\u003eIn contrast to that findings, a large multicenter study conducted in Italy involving 2,362 adult patients reported a median diagnostic delay of only 8 months (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e). In this study, it was reported that 398 (17.5%) celiac patients were misdiagnosed at least once before receiving a definitive diagnosis. The most common misdiagnosis is irritable bowel syndrome. Since our study was prospective, there were no patients with misdiagnosis. But the median diagnostic delay time is similar to that study.\\u003c/p\\u003e\\u003cp\\u003eThe current study has some limitations. First; there is a small number of centers. Secondly, there is a small number of patients participated in the study.\\u003c/p\\u003e\\u003cp\\u003e The strength of the current study is that it is a prospective study and centers from different regions from our country participated in the study. Due to that, we think this may reflect our country's data.\\u003c/p\\u003e\"},{\"header\":\"CONCLUSIONS\",\"content\":\"\\u003cp\\u003eWe detected that the median delay from onset of first symptoms to diagnosis was 7.30 months. It is promising that the delay in diagnosis is relatively low compared to the literature. Since CD has serious long-term complications, we aim to diagnose it even earlier in future. Diagnostic delays in CD significantly and adversely impact patients' quality of life and overall health. Consequently, diagnostic delay represents a public health concern. One of the primary reasons for diagnostic delay may be the limited awareness of CD among healthcare professionals. Therefore, increasing awareness through online seminars, dissemination of public service announcements, and implementation of comparable educational initiatives are essential. Additionally, screening for CD in high-risk groups can help reduce diagnostic delays.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eceliac disease\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eGFD\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003egluten-free diet\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003etTG\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003etissue transglutaminase antibody\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate:\\u0026nbsp;\\u003c/strong\\u003eWritten informed consent was obtained from both the children and their parents (all parents of participing children who were under 16). The study was approved by the Local Clinical Research Ethics Board (Sanko University, Gaziantep, Turkey, June 2, 2021/06). Also, the study was conducted in accordance with the ethical standards in the Declaration of Helsinki.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication:\\u0026nbsp;\\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials:\\u0026nbsp;\\u003c/strong\\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests:\\u0026nbsp;\\u003c/strong\\u003eThe authors declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFundings:\\u0026nbsp;\\u003c/strong\\u003eNone\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors contributions:\\u0026nbsp;\\u003c/strong\\u003eSahin Y, designed the study, collected the data, analyzed the data, interpreted the data,\\u0026nbsp;conception, and statistical analysis,\\u0026nbsp;and wrote the manuscript; Sevinc E, collected the data, analyzed the data, interpreted the data,\\u0026nbsp;and statistical analysis,\\u0026nbsp;and wrote the manuscript; Bayrak NA, Varol FI, Akbulut UA, and Bukulmez A collected the data, and analyzed the data; All authors had read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u0026nbsp;\\u003c/strong\\u003eWe thank Kadriye Nil Bezci, MD for performing endoscopy on some patients in Gaziantep.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eSahin Y. Celiac disease in children: A review of the literature. World J Clin Pediatr 2021; 10: 53-71.\\u003c/li\\u003e\\n\\u003cli\\u003eTarar ZI, Zafar MU, Farooq U, Basar O, Tahan V, Daglilar E. The progression of celiac disease, diagnostic modalities, and treatment options. J Investig Med High Impact Case Rep. 2021; 9: 23247096211053702.\\u003c/li\\u003e\\n\\u003cli\\u003eCrehu\\u0026aacute;-Gaudiza E, Barr\\u0026eacute;s Fern\\u0026aacute;ndez A, Jovan\\u0026iacute; Casano C, Latorre Tejerina M, Largo Blanco EM, Moreno Ruiz MA, et al. Diagnosis of celiac disease in clinical practice: Present and future. An Pediatr (Engl Ed). 2021; 94: 223-229. \\u003c/li\\u003e\\n\\u003cli\\u003eGreen PHR, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol. 2001; 96: 126-31.\\u003c/li\\u003e\\n\\u003cli\\u003eWest J, Logan RF, Hill PG, Lloyd A, Lewis S, Hubbard R, et al. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut. 2003; 52: 960-5.\\u003c/li\\u003e\\n\\u003cli\\u003eGray AM, Papanicolas IN. Impact of symptoms on quality of life before and after diagnosis of coeliac disease: results from a UK population survey. BMC Health Serv Res 2010; 10: 1-7.\\u003c/li\\u003e\\n\\u003cli\\u003eNorstr\\u0026ouml;m F, Lindholm L, Sandstr\\u0026ouml;m O, Nordyke K, Ivarsson A. Delay to celiac disease diagnosis and its implications for health-related quality of life. BMC Gastroenterol 2011; 11: 1-8.\\u003c/li\\u003e\\n\\u003cli\\u003ePaez MA, Gramelspacher AM, Sinacore J, Winterfield L, Venu M. Delay in diagnosis of celiac disease in patients without gastrointestinal complaints. Am J Med 2017; 130: 1318-23.\\u003c/li\\u003e\\n\\u003cli\\u003eCosnes J, Nion-Larmurier I. Complications of celiac disease. Pathol Biol (Paris) 2013; 61: e21-6.\\u003c/li\\u003e\\n\\u003cli\\u003eIvanova M, Bottiglieri L, Sajjadi E, Venetis K, Fusco N. Malignancies in patients with celiac disease: Diagnostic challenges and molecular advances. Genes (Basel). 2023 Jan 31; 14: 376.\\u003c/li\\u003e\\n\\u003cli\\u003eYl\\u0026ouml;nen V, Lindfors K, Repo M, Huhtala H, Fuchs V, Saavalainen P, et al. Non-biopsy serology-based diagnosis of celiac disease in adults is accurrate with different comercial kits and pre-test probabilities. Nutrients 2020; 12: 2736.\\u003c/li\\u003e\\n\\u003cli\\u003eRiznik P, De Leo L, Dolinsek J, Gyimesi J, Klemenak M, Koletzko B, et al. Diagnostic delay in children with coeliac disease in the Central European Region. J Pediatr Gastroenterol Nutr. 2019; 69: 443-448.\\u003c/li\\u003e\\n\\u003cli\\u003eKho A, Whitehead M, Day AS. Coeliac disease in children in Christchurch, New Zealand: Presentation and patterns from 2000\\u0026ndash;2010. World J Clin Pediatr. 2015; 4: 148\\u0026ndash;54.\\u003c/li\\u003e\\n\\u003cli\\u003eVan Kalleveen MW, de Meij T, Plotz FB. Clinical spectrum of paediatric coeliac disease: a 10-year single-centre experience. Eur J Pediatr. 2018; 177: 593-602.\\u003c/li\\u003e\\n\\u003cli\\u003eFasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001; 120: 636-51.\\u003c/li\\u003e\\n\\u003cli\\u003eDhar J, Samanta J, Sharma M, Kumar S, Sinha SK, Kochar R. Impact of delay in diagnosis in patients with celiac disease: A study of 570 patients at a tertiary care center. Indian J Gasstroenterol 2022; 41: 30-36.\\u003c/li\\u003e\\n\\u003cli\\u003eFuchs V, Kurppa K, Huhtala H, Collin P, M\\u0026auml;ki M, Kaukinen K. Factors associated with long diagnostic delay in celiac disease. Scand J Gastroenterol. 2014; 49: 1304-10.\\u003c/li\\u003e\\n\\u003cli\\u003eK\\u0026aring;rhus LL, Hansen S, Rumessen JJ, Linneberg A. Diagnostic Delay in Coeliac Disease: A Survey among Danish Patients. Can J Gastroenterol Hepatol 2022; 2022: 5997624.\\u003c/li\\u003e\\n\\u003cli\\u003eMehta S, Agarwal A, Pachisia AV, Singh A, Dang S, Vignesh D, et al. Impact of delay in the diagnosis on the severity of celiac disease. J Gastroenterol Hepatol. 2024; 39: 256-263.\\u003c/li\\u003e\\n\\u003cli\\u003eZipser RD, Patel S, Yahya KZ et al. Presentations of adult celiac disease in a nationwide patient support group. Dig Dis Sci 2003; 48: 761-4.\\u003c/li\\u003e\\n\\u003cli\\u003eLenti MV, Aronico N, Bianchi PI et al. Diagnostic delay in adult coeliac disease: an Italian multicentre study. Dig Liver Dis 2023; 55: 743\\u0026ndash;50.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTables 1 to 3 are available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-gastroenterology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bmge\",\"sideBox\":\"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bmge/default.aspx\",\"title\":\"BMC Gastroenterology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"celiac disease, children, diagnostic delay\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7133140/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7133140/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eObjectives\\u003c/h2\\u003e\\u003cp\\u003eThere is few studies conducted investigating diagnostic delay in children with celiac disease (CD). A better understanding of the factors associated with diagnostic delay and the development of strategies to reduce it are important in preventing long-term complications related to the disease. This study aimed to determine the average diagnostic delay in children with CD and to investigate possible underlying factors associated with diagnostic delay.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e\\u003cp\\u003eA prospective screening program was performed in children with CD at the seven clinical centers operating in Turkey within the Focus IN CD project between June 2021 and June 2023. Paediatric gastroenterologists were asked to complete a web-based questionnaire about CD.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e\\u003cp\\u003eThe median ages of the 188 celiac patients (66 male; 35%) were 8,33 (1,34\\u0026thinsp;\\u0026minus;\\u0026thinsp;18,17) years. The median diagnostic delay was 7,3 months (0,03-133,9). Upon patient with CD were categorised according to OSLO criteria, The median delay for classic CD group, nonclassic CD group and silent CD group were found 14.31 (11.14\\u0026ndash;17.47), 11.98 (2.52\\u0026ndash;21.44) and 9.49 (3.48\\u0026ndash;15.49) month respectively. There were no significant differences between the patients with classic CD group and the nonclassic CD group and silent CD group (p\\u0026thinsp;=\\u0026thinsp;1.000 and p\\u0026thinsp;=\\u0026thinsp;0,939, respectively)\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e\\u003cp\\u003eThe study revealed that median diagnostic delay was 7,3 months. Furthermore there were no significant differences clinical subtypes of CD. In order to minimize the delay in diagnosis, it may be a solution to rise community-based awareness of CD and better informing pediatricians and family physicians about CD.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Diagnostic Delay in Children With Coeliac Disease: A national multicentre study in Turkey\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-08-12 10:42:54\",\"doi\":\"10.21203/rs.3.rs-7133140/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2025-09-05T06:36:32+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-09-01T21:43:20+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"328284292571196730104535982538159765526\",\"date\":\"2025-09-01T08:35:19+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"196499435488643899186859883614316151851\",\"date\":\"2025-08-27T04:02:25+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"304007273109653550236457987303120638\",\"date\":\"2025-08-26T18:19:53+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"75288307653190683689516714795441658387\",\"date\":\"2025-08-26T05:23:31+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-08-25T16:03:25+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"183351926902875928650816547038852517265\",\"date\":\"2025-08-25T10:46:26+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"125210314385841866084427500376369562327\",\"date\":\"2025-08-25T08:09:46+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"108608257520336664322474867128382496361\",\"date\":\"2025-08-10T17:04:23+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"307057118051650113330662598321475925348\",\"date\":\"2025-08-06T20:37:44+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-08-06T20:35:01+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-08-06T18:53:13+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2025-08-01T16:18:46+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-08-01T12:12:49+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Gastroenterology\",\"date\":\"2025-08-01T12:10:08+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-gastroenterology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bmge\",\"sideBox\":\"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bmge/default.aspx\",\"title\":\"BMC Gastroenterology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"6ac53eff-1e45-4b5b-9e0b-2db1273132bb\",\"owner\":[],\"postedDate\":\"August 12th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-01-26T16:08:44+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-7133140\",\"link\":\"https://doi.org/10.1186/s12876-026-04639-2\",\"journal\":{\"identity\":\"bmc-gastroenterology\",\"isVorOnly\":false,\"title\":\"BMC Gastroenterology\"},\"publishedOn\":\"2026-01-22 15:58:31\",\"publishedOnDateReadable\":\"January 22nd, 2026\"},\"versionCreatedAt\":\"2025-08-12 10:42:54\",\"video\":\"\",\"vorDoi\":\"10.1186/s12876-026-04639-2\",\"vorDoiUrl\":\"https://doi.org/10.1186/s12876-026-04639-2\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7133140\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7133140\",\"identity\":\"rs-7133140\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}