Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders

Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders | 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 Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders Tut Galai, Hadar Moran-Lev, Shlomi Cohen, Amir Ben-Tov, Dina Levy, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.20433/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 May, 2020 Read the published version in BMC Pediatrics → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background : Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders. Methods: We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85 th percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. Results : Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight. Conclusions: Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP. Pediatrics Gastroenterology & Hepatology functional gastrointestinal disorders children irritable bowel syndrome overweight obesity. Background Functional gastrointestinal disorders (FGID) are very common clinical conditions encountered in day-to-day clinical pediatric gastroenterology practice (1). Increased knowledge of the pathophysiology of FGID in the last decade has led to the design of a biopsychosocial model in which genetic, physiological, and psychological factors interact (2). The diagnosis of FGID is clinical and based on the Rome diagnostic criteria, which have evolved during the last decades to form the newest set, the Rome IV criteria which was issued in 2016 (3). Several epidemiological studies using the Rome III and Rome IV criteria showed that FGID related to abdominal pain are highly prevalent (4,5). According to the Rome IV criteria, the term “abdominal pain related functional gastrointestinal disorders” has been changed to “functional abdominal pain disorders” and it includes functional dyspepsia (FD), irritable bowel syndrome (IBS), abdominal migraine, and functional abdominal pain not otherwise specified (functional abdominal pain NOS) (3). Childhood obesity is a serious and urgent public health problem that is associated with physical and psychological comorbidities (6). The bidirectional association between obesity and FGID has been described in previous studies, however, some of them are limited by a lack of control groups or outdated diagnostic criteria (7-9), and none of them was based on ROME IV criteria. The primary aim of this study was to define the association between obesity and functional abdominal pain (FAP) disorders in children according to the Rome IV criteria compared with a population control, and to describe and compare clinical characteristics of children with overweight/obesity with those of healthy weight and FAP disorders. Methods All study procedures were approved by the institutional review board of the Tel Aviv Medical Center (Helsinki Committee), and parental informed consent was obtained for all participants. Study Design and Participants We conducted a retrospective study of 2- to 18-year-old children with a clinical diagnosis of FAP disorders that were followed-up in the Pediatric Gastroenterology Unit at the "Dana-Dwek" Children's Hospital, Tel Aviv, Israel, between January 2016 and October 2018. The Pediatric Gastroenterology unit is an outpatient clinic at our hospital, which is a tertiary referral center for pediatric gastroenterology. The patients were identified through the local electronic health records database. After the patients with clinical diagnosis of FAP were identified from the medical records, we performed an objective evaluation of the compatibility of their diagnosis with the ROME IV criteria (3). Patients that did not fulfill these criteria were excluded from the study, as were patients with missing anthropometric data. Body mass index (BMI) percentiles were defined by the CDC standards (10). Patients with BMIs ≥85 th percentile were designated as being overweight or obese. A population control group was obtained from the 2015-2016 Israel national health survey (11). The Israeli health survey is a national survey, conducted every 3-4 years by the ministry of health of Israel, that aims to investigate health and nutrition status among the Israeli population by a representative sample of children and adults. The data in the survey is presented according to age groups (2-11 and 12-18 years of age) and gender. Data Collection We retrospectively reviewed the patients' records and collected demographic data consisting of age, gender, location and duration of symptoms (abdominal pain, vomiting, diarrhea, heartburn) as well as anthropometric data (weight, height, BMI). We also reviewed imaging and endoscopies studies, hospitalizations, dietitian consultations, nutrition recommendations, and follow-up durations. Data Statistical Analysis Categorical variables were reported as frequency and percentage. Continuous variables were evaluated for normal distribution using a histogram and Kolmogorov–Smirnov test. Since none of the continuous variables were normally distributed, they were reported as median and interquartile range (IQR). Overweight proportion was compared to the published data using the one-sample binomial test. Characteristics of overweight and non-overweight children were compared using the Chi-square test or Fisher's exact test for the categorical variables, and the Mann-Whitney test was used for the continuous and ordinal variables. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. SPSS was used for all statistical analyses (IBM SPSS Statistics, version 25, IBM Corp., Armonk, NY, USA). Results Demographic and Clinical Data A total of 274 children were identified as having the diagnosis of FAP. Forty-eight children who did not meet the ROME IV criteria and 53 children with missing data were excluded, leaving a total of 173 children for final analysis. Of these children, 114 (65.8%) were females, and the group’s median age was 11.5 (IQR 7.9-14.5) years, nearly all of them were from Israeli Jewish origin (170 patients, 98.3%). The functional disorders were functional abdominal pain NOS ( n = 71, 41%), IBS ( n = 67, 38.8%), and FD ( n = 35, 20.2%). No abdominal migraine cases were identified. The median duration of the abdominal pain was 8 months (IQR 4-20), the median BMI percentile was 64 (IQR 26.7-86.5), and the median follow-up duration was 2.1 months (IQR 0-6). The demographic and clinical data are presented in Table 1. Sixty children (36.4%) underwent gastroscopy, 13 (7.5%) underwent colonoscopy, and 132 (76.3%) underwent imaging studies, of whom 115 (66.5%) had an abdominal ultrasound and 17 (9.8%) had an abdominal computerized tomography or a magnetic resonance enterography. Ninety-nine children (57.2%) received medications: 50 (28.9%) were treated with stool softeners, 38 (22%) with proton pump inhibitors (PPI), and 11 (6.4%) with probiotics. No gender difference was noticed in medication use. However, significantly more children with FD were treated with PPI compared to children with IBS and functional abdominal pain NOS (57.1%, 13.4% and 12.7%, respectively, P<0.001). Twenty children (11.5%) were hospitalized due to FAP. In addition, 105 children (60.6%) were given general balanced dietary recommendations from the physician and 46 (26.5%) children received formal dietitian consultations. Specific dietary recommendations were given as follows: high fiber ( n = 38, 22%), reduced simple carbohydrates ( n = 24, 13.9%) or lactose free ( n = 19, 11%). Overweight/obese vs. normal weight in FAP group Of all 173 children, 53 children (30.6%) were accounted as overweight/obese. Among these 53 children, 20 were truly obese (37.7%), 15 (28.3%) boys and 38 (71.7%) girls. The distribution of FAP disorders among the children with overweight/obesity was as follow; 22 (41.5%) with IBS, 16 (30.2%) with functional abdominal pain-NOS and 15 (28.3%) with FD (Table 1). No significant relation was found between obesity and FAP subgroups. Children with FAP and overweight/obesity disorders were older (12.4 (9.8-15.3) vs. 10.8 (7.4-14.1), p=0.04), had more hospitalizations due to FAP (20.8% vs. 7.5% p=0.01), were treated more with PPI (26.4% vs. 20%, p=0.05) and had more dietitian consultations (43.4% vs. 19.2%, p=0.001) compared with children with FAP and normal weight (Table 1). There was no significant difference in gender, endoscopies and imaging studies performance, follow up duration and nutrition recommendations between the groups. The FAP Group vs. the Controls The 6432 controls were divided into two age groups, one 2-11 years of age and one 12-18 years of age. The younger age group included 1792 children, of whom 919 (51.3%) were boys and 873 (48.7%) were girls. There were 299 children (16.7%) in the young age group who were designated as having overweight/obesity. The older age group of 4640 children included 2223 (47.9%) boys and 2417 (52%) girls, among whom 1433 (30.8%) were designated as having overweight/obesity (Table 2). The 2- to 11-year-old girls with FAP had a significantly higher prevalence of overweight/obesity compared with the controls in that age range (70.6% vs. 48.7%, p = 0.04) (Table 2). In addition, the 12- to 18-year old children with FAP had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30.8%, respectively, p = 0.04), and specifically in girls (42.9% vs. 29.2%, p = 0.01) in that age range. There was no significant difference between prevalence of overweight/obesity of boys with FAP in any age group compared to controls. Discussion The association between obesity and FAP according to the updated ROME IV criteria had not been investigated before. In the current study, our analysis of that association revealed a higher prevalence of overweight/obesity among adolescents with FAP disorders compared to an age- and sex-matched control population. Our results are in line with studies that had demonstrated a correlation between body weight and FGID. Teitelbaum et al (8) showed a greater percentage of children with obesity and constipation, gastroesophageal reflux disease, IBS, encopresis and FAP compared with children with healthy weight. In their study, functional disorders were assigned based on ROME II criteria without specification of subtypes of FAP. From another point of view, Bonilla et al (9) described a cohort from 2007-2008 with a prevalence of 20.2% obesity in patients with FGID, however, no comparison to healthy control group was performed. They showed that obesity was associated with poor outcome and disability at long term follow up. In our study the prevalence of overweight/obesity was higher, probably attributed to the combination of children with overweight and obesity as one group or to the increase in prevalence of obesity in the western world as part of the obesity epidemic. Other studies demonstrated higher percentages of recurrent abdominal pain (12) and FGID (7) in children with obesity. However, Malaty et al (12) used a non-validated questionnaire and the latter study was based on ROME III criteria for diagnosis of functional disorders. Several factors may explain the association between obesity and FAP disorders. Dietary habits are a major factor in obesity development and previous studies showed the association between increased consumption of carbohydrates and high body weight (13, 14, 15). Carbohydrate malabsorption may cause gastrointestinal symptoms via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation (16). Moreover, there is some evidence that a low-FODMAP diet is effective in reducing IBS symptoms (17, 18). Recently, Schnabel et al showed an association between ultra-processed food (UPF) consumption and functional gastrointestinal disorders. In this large French cohort, an increase in UPF, which is characterized by high density of saturated fatty acids, sugar, sodium and low content of protective nutrients such as fibers, was associated with a higher risk of IBS. They also found that UPF consumption was associated with higher BMI. (19). In addition to dietary habits, sedentary lifestyle and lack of physical activity could be related to both obesity and functional pain (20). A potential association between obesity, FGID and gastrointestinal motility disorders has also been described. Delayed gastric emptying and impaired antral motility were found in children with RAP, FAP, IBS or functional dys­pepsia (21, 22). Several studies have shown delayed gastric emptying and gastric and gallbladder dysmotility in the individuals with obesity (23, 24). This may be attributed to increased gastric distention in the obese causing poor fundal and antral tone (25), altered sensitivity of mechanoreceptors in the stomach musculature (26) and abnormal perception of satiety signals (27). Another association between obesity and FGID is the gut microbiota. Increased risk of small intestinal bacterial overgrowth (28) and different gut microbiota composition (29) in obesity has been reported which might contribute to gastrointestinal dysmotility, excessive fermentation, altered visceral perception and gut permeability with their metabolites leading to pain-predominant FGID (30, 31). Finally, obesity and FGID share common psychological comorbidities, such as stress, depression, and anxiety, which can contribute to each other's development and aggravate each other (32,33,34). The higher prevalence of overweight/obesity in females with FAP compared to controls may be attributed to several factors. Females are more prone to several gastrointestinal motility disorders, such as delayed gastric emptying, compared to males (35,36). It has been suggested that this difference may be caused by female ovarian hormones. Gender differences in intestinal microbiome in addition to microbiome difference between children with overweight/obesity and children with healthy weight (37) may serve as an alternative explanation. Our study has demonstrated a few significant differences between children with FAP having overweight/obesity compared to normal weight children. We found that children with overweight/obesity had more hospitalizations attributed to their abdominal pain compared with children with healthy weight, as described in other studies which suggested that pediatric obesity contributes significantly to increased health care utilization in children (38, 39). A possible explanation to increased health care utilization in children with obesity is comorbidities of obesity (38). In addition, children with obesity might be more symptomatic compared to children with normal weight (40). We also found that obese children with FAP are treated more frequently with PPI than non-obese children with FAP. Parkman et al (36) reported that patients with obesity and idiopathic gastroparesis tend to be more symptomatic compared to patients with healthy weight. Whether this is true to patients with FAP is to be elucidated. Although no relation between FAP subgroups and obesity was established in this study, children with FD were treated more frequently with PPI, in line with the ROME IV recommendations (3), compared to other FAP subgroups. Generally, overuse of PPI has been increasing in the last decade in hospitalized and ambulatory patients and their prescription continues to grow in all western countries (41). The clinical implications of the findings of our current study relate to the management of children with overweight/obesity and FGID. Although this study could not indicate causality between obesity and FAP, the findings support a relation between these conditions. The treatment protocol of children with obesity and FAP should also focus on guidance for more thorough nutritional assessment targeted towards weight reduction together with other lifestyle changes (e.g., increase in physical activities) that may improve symptoms and prevent or at least minimize the need for medications and hospitalizations. To the best of our knowledge, this is the first study to show an association between obesity and FAP diagnosed in children according to the updated ROME IV criteria for diagnosis of FAP, which was made by a pediatric gastroenterologist in a clinic setting and not by collecting information from a self-administered questionnaire. This study is limited by its retrospective nature, missing more precise data on skinfold measurements, body composition, and other parameters. In addition, our control group might include children with FAP disorders, although we believe that due to the high number of children included, the percentage of children with FAP disorders would be similar to the general population. Lastly, a part of children with diagnosis of FAP in the medical records did not fulfil the ROME IV criteria and therefore were excluded. In real life, some degree of incompatibility between clinical diagnosis and formal criteria may be anticipated. Another explanation is the difference between ROME IV and ROME III criteria, that was one of the rationales to conduct the current study. Conclusions Adolescents with FAP disorders have a higher prevalence of overweight/obesity compared with controls in the general population. Children with FAP and overweight/obesity have more hospitalizations and medical treatment with PPI compared to children with FAP disorders who are of normal weight. Heightened awareness of these findings might improve treatment planning and management to meet the needs of children with overweight/obesity and FAP. Further studies should focus on the interrelationship between FGID and obesity and specifically on the pathophysiologic mechanisms between these conditions, and also to investigate the effect of weight reduction on FAP symptoms. Abbreviations FGID - Functional gastrointestinal disorders FD- functional dyspepsia IBS- irritable bowel syndrome NOS- not otherwise specified FAP- functional abdominal pain BMI- Body mass index IQR- interquartile range PPI- proton pump inhibitors Declarations Ethics approval and consent to participate All study procedures were approved by the institutional review board of the Tel Aviv Medical Center (Helsinki Committee), and written parental informed consent was obtained for all participants.( 0402-14-TLV) 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 that they have no competing interests Funding No funding to declare. Authors' contributions TG, HML and AYF formulated the research question and designed the study. TG, ABT, YW, AA analyzed the data, and wrote the manuscript. OS, AA, YW collected the data. DL is the registered dietitian in this study; SC supervised the statistical analysis, and revised the manuscript. All authors critically reviewed the manuscript and approved the final version submitted for publication . Acknowledgements : Not Applicable Short title : Obesity in children with functional abdominal pain Transparency declaration: The lead author affirms that this manuscript is an honest, accurate and transparent account of the study being reported. References Rouster AS, Karpinski AC, Silver D, et al. Functional gastrointestinal disorders dominate pediatric gastroenterology outpatient practice. J Pediatr Gastroenterol Nutr 2016;62:847-851. Korterink J, Devanarayana NM, Rajindrajith S, et al. Childhood functional abdominal pain: mechanisms and management. Nat Rev Gastroenterol Hepatol 2015;12:159-171. Rasquin A , Di Lorenzo C , Forbes D , et al. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 2016;150:1456-1468. Devanarayana NM , Rajindrajith S , Perera MS, et al. Association between functional gastrointestinal diseases and exposure to abuse in teenagers. J Trop Pediatr 2014;60:386-392. Saps M, Velasco-Benitez CA, Langshaw AH, et al. Prevalence of functional gastrointestinal disorders in children and adolescents: comparison between Rome III and Rome IV criteria. J Pediatr 2018;199:212-216. Sanders RH , Han A , Baker JS , et al. Childhood obesity and its physical and psychological co-morbidities: a systematic review of Australian children and adolescents. Eur J Pediatr 2015; 174:715-746. Tambucci R, Quitadamo P, Ambrosi M, et al. Association between obesity/overweight and functional gastrointestinal disorders in children. J Pediatr Gastroenterol Nutr 2019; 68:517-520. Teitelbaum JE, Sinha P, Micale M, et al. Obesity is related to multiple functional abdominal diseases. J Pediatr 2009; 154:444-446. Bonilla S , Wang D , Saps M . Obesity predicts persistence of pain in children with functional gastrointestinal disorders. Int J Obes (Lond) 2011; 35:517-521. https://www.cdc.gov/growthcharts/clinical_charts.htm https://www.health.gov.il/UnitsOffice/ICDC/mabat/Pages/default.aspx Malaty HM , Abudayyeh S , Fraley K , et al. Recurrent abdominal pain in school children: effect of obesity and diet. Acta Paediatr 2007; 96:572-576. Emmett PM , Jones LR . Diet, growth, and obesity development throughout childhood in the Avon Longitudinal Study of Parents and Children. Nutr Rev 2015; 73:175-206. Te Morenga L , Mallard S , Mann J . Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 2012 15; 346: e7492. Dello Russo M , Ahrens W , De Henauw S , et al. IDEFICS Consortium . The Impact of Adding Sugars to Milk and Fruit on Adiposity and Diet Quality in Children: A Cross-Sectional and Longitudinal Analysis of the Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) Study. Nutrients . 2018; 21;10:1350. Chumpitazi BP , Shulman RJ . Dietary Carbohydrates and Childhood Functional Abdominal Pain. Ann Nutr Metab 2016; 68:8-17. Shepherd SJ , Lomer MC , Gibson PR . Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol 2013; 108:707-17. Staudacher HM , Whelan K , Irving PM , et Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet 2011; 24:487-495. Schnabel L , Buscail C , Sabate JM , et al. Association Between Ultra-Processed Food Consumption and Functional Gastrointestinal Disorders: Results From the French NutriNet-Santé Cohort. JPGN 2013; 57: 141–148. Rabbitts JA, Holley AL, Karlson CW, Palermo TM. Bidirectional associations between pain and physical activity in adolescents. Clin J Pain 2014;30:251–8. Devanarayana NM , Rajindrajith S , Bandara C , et al. Ultrasonographic assessment of liquid gastric emptying and antral motility according to the subtypes of irritable bowel syndrome in children. J Pediatr Gastroenterol Nutr 2013; 56(4):443-448. Devanarayana NM , Rajindrajith S , Perera MS , et al. Gastric emptying and antral motility parameters in children with functional dyspepsia: association with symptom severity. J Gastroenterol Hepatol 2013; 28:1161-1166. Di Ciaula A , Wang DQ , Portincasa P . Gallbladder and gastric motility in obese newborns, pre-adolescents and adults. J Gastroenterol Hepatol 2012; 27:1298-1305. Jackson SJ , Leahy FE , McGowan AA , et al. Delayed gastric emptying in the obese: an assessment using the non-invasive (13) C-octanoic acid breath test. Diabetes Obes Metab 2004; 6:264-270. Horowitz M, Collins PJ, Cook DJ et al. Abnormalities of gastric emptying in obese patients. Int J Obes. 1983;7:415-421. Maddox A , Horowitz M , Wishart J , et al. Gastric and oesophageal emptying in obesity. Scand J Gastroenterol 1989; 24:593-598. Horowitz M , Collins PJ , Shearman DJ . Effect of increasing the caloric/osmotic content of the liquid component of a mixed solid and liquid meal on gastric emptying in obese subjects. Hum Nutr Clin Nutr 1986; 40:51-56. Roland BC , Lee D , Miller LS , et al. Obesity increases the risk of small intestinal bacterial overgrowth (SIBO). Neurogastroenterology&Motility 2018;3:e13199. Hou YP, He QQ, Ouyang HM, et al. Human Gut Microbiota Associated with Obesity in Chinese Children and Adolescents. Biomed Res Int. 2017; 758598. Rhee, S. H., Pothoulakis, C. & Mayer, E. A. Principles and clinical implications of the brain–gut–enteric microbiota axis. Rev. Gastroenterol. Hepatol. 2009; 6:306–314 Ohman, L. & Simren, M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). Curr Gastroenterol Rep 2013; 15: 323. Topçu S , Orhon FŞ , Tayfun M , et al. Anxiety, depression and self-esteem levels in obese children: a case-control study. J Pediatr Endocrinol Metab 2016; 29:357-361. Shin NY , Shin MS . Body dissatisfaction, self-esteem, and depression in obese Korean children. J Pediatr 2008;152: 502-506. CampoJV , Gilchrist RH . Psychiatric comorbidity and functional abdominal pain. Pediatr Ann 2009; 38:283-287. Zia JK, Heitkemper MM. Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease. Gastroenterol Clin North Am . 2016;45(2):239-51. Parkman HP, Yates K, Hasler WL et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology 2011;140(1):101-15. Gao X, Jia R, Xie L et al. A study of the correlation between obesity and intestinal flora in school-age children. Sci Rep 2018;8(1):14511. Hampl SE , Carroll CA , Simon SD , et al. Resource utilization and expenditures for overweight and obese children. Arch Pediatr Adolesc Med . 2007; 161:11-14. Trasande L , Chatterjee S . The impact of obesity on health service utilization and costs in childhood. Obesity .2009; 17:1749-1754. Grout RW, Thompson-Fleming R, Carroll AE, et al. Prevalence of pain reports in pediatric primary care and association with demographics, body mass index, and exam findings: a cross-sectional study. BMC Pediatr 2018;18(1):363. Lanas A . We Are Using Too Many PPIs, and We Need to Stop: A European Perspective. Am J Gastroenterol 2016; 111:1085-1086. Tables Table 1. Demographic and clinical data Study cohort N=173 Normal or underweight N=120 (69.3%) Overweight or obese N=53 (30.7%) P Age (years) 11.5 (7.9-14.5) 10.8 (7.4-14.1) 12.4 (9.8-15.3) 0.04 Females 114 (65.8%) 76 (63.3%) 38 (71.7%) 0.29 FAP disorders: Functional abdominal pain NOS Irritable bowel syndrome Functional dyspepsia 71 (41%) 67 (38.8%) 35 (20.2%) 55 (45.8%) 45 (37.5%) 20 (16.7%) 16 (30.2%) 22 (41.5%) 15 (28.3%) 0.07 Hospitalizations 20 (11.6%) 9 (7.5%) 11 (20.8%) 0.01 Proton pump inhibitors treatment 38 (22%) 24 (20%) 14 (26.4%) 0.05 Dietitian consultations 46 (26.6%) 23 (19.2%) 23 (43.4%) 0.001 Table 2. Overweight Patients in the FAP and Control Groups by Age and Gender P Control N=4640 FAP group N=81 Children 12-18 years old 0.04 1433 (30.8%) 32 (39.5%) Total overweight/obese 0.44 2223 (47.9%) 726 (32.6%) 32 (39.5%) 11 (34.4%) Males Overweight/obese males 0.01 2417 (52%) 707 (29.2%) 49 (60.4%) 21 (42.9%) Females Overweight/obese females P Control N=1792 FAP group N=92 Children 2-11 years old 0.07 299 (16.7%) 21 (22.8%) Total overweight/obese 0.5 919 (51.3%) 148 (16.1%) 27 (29.3%) 4 (14.8%) Males Overweight/obese males 0.04 873 (48.7%) 151 (17.3%) 65 (70.6%) 17 (26.2%) Females Overweight/obese females Cite Share Download PDF Status: Published Journal Publication published 06 May, 2020 Read the published version in BMC Pediatrics → Version 3 posted Editorial decision: Accept 28 Apr, 2020 Editor assigned by journal 27 Apr, 2020 Editor invited by journal 26 Apr, 2020 Submission checks completed at journal 06 Jan, 2020 You are reading this latest preprint version Show more versions 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. 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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-11040","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":530646,"identity":"24f54dd0-7afa-40fd-87a1-ab93feb5b58e","order_by":1,"name":"Tut Galai","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tut","middleName":"","lastName":"Galai","suffix":""},{"id":530647,"identity":"5d00c33d-6e70-4ebc-b180-e626ffbf1071","order_by":2,"name":"Hadar Moran-Lev","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hadar","middleName":"","lastName":"Moran-Lev","suffix":""},{"id":530648,"identity":"d1499a64-55eb-4c8b-bef0-23bf3cff5f42","order_by":3,"name":"Shlomi Cohen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYDACCeYGBgYDBgZ+BhADCg48wKuFEaJFso0RSUsCQS1AYHAMSQsDPi3ysxsbH90osJMzvt/YJnWjhsGuXyKBEa8tBncONhvnGCQbmx1jbJPOOcaQPHNGAn6HGUgkAlUaHEjcdoyx2Ti3gSHZ4MwB/FrkZ0C1bG4jVgvDDaiWDWyMjY+BWuwMjjcQcNiNRIhfJI4lNj7OOSaRINne2EDAYckHH+f8sZPjbz584HBOjY09PzPz4Q8f8DkMDUgkNjAgRxAxwJ405aNgFIyCUTASAAA4O1A4PHsCPAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6190-3217","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Shlomi","middleName":"","lastName":"Cohen","suffix":""},{"id":530649,"identity":"8f99fd8d-62ab-4533-8ca3-3dffa2dff6d6","order_by":4,"name":"Amir Ben-Tov","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Ben-Tov","suffix":""},{"id":530650,"identity":"76dd46eb-f0b7-4f73-86a3-20fcc0f1dc42","order_by":5,"name":"Dina Levy","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dina","middleName":"","lastName":"Levy","suffix":""},{"id":530651,"identity":"8079443d-3fd1-41a1-82f3-008bd72868d4","order_by":6,"name":"Yael Weintraub","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yael","middleName":"","lastName":"Weintraub","suffix":""},{"id":530652,"identity":"90f760fb-2074-47ae-8987-0234b7014f84","order_by":7,"name":"Achiya Amir","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Achiya","middleName":"","lastName":"Amir","suffix":""},{"id":530653,"identity":"5a0cef9f-381e-4102-927c-2679aeb67517","order_by":8,"name":"Or Segev","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Or","middleName":"","lastName":"Segev","suffix":""},{"id":530654,"identity":"b1d30298-6196-476d-895f-344b489d9472","order_by":9,"name":"Anat Yerushalmy-Feler","email":"","orcid":"","institution":"Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anat","middleName":"","lastName":"Yerushalmy-Feler","suffix":""}],"badges":[],"createdAt":"2020-01-07 14:38:54","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.2.20433/v3","doiUrl":"https://doi.org/10.21203/rs.2.20433/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-020-02106-9","type":"published","date":"2020-05-06T20:33:40+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":13503574,"identity":"fefb92a6-cd60-4573-a909-6f288f6815d9","added_by":"auto","created_at":"2021-09-16 23:19:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":373278,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-11040/v3/496bfd60-87df-4ece-94a9-734e6efc76a2.pdf"}],"financialInterests":"","formattedTitle":"Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders","fulltext":[{"header":"Background","content":"\u003cp\u003eFunctional gastrointestinal disorders (FGID) are very common clinical conditions encountered in day-to-day clinical pediatric gastroenterology practice (1). Increased knowledge of the pathophysiology of FGID in the last decade has led to the design of a biopsychosocial model in which genetic, physiological, and psychological factors interact (2). The diagnosis of FGID is clinical and based on the Rome diagnostic criteria, which have evolved during the last decades to form the newest set, the Rome IV criteria which was issued in 2016 (3). Several epidemiological studies using the Rome III and Rome IV criteria showed that FGID related to abdominal pain are highly prevalent (4,5). According to the Rome IV criteria, the term \u0026ldquo;abdominal pain related functional gastrointestinal disorders\u0026rdquo; has been changed to \u0026ldquo;functional abdominal pain disorders\u0026rdquo; and it includes functional dyspepsia (FD), irritable bowel syndrome (IBS), abdominal migraine, and functional abdominal pain not otherwise specified (functional abdominal pain NOS) (3).\u003c/p\u003e\n\u003cp\u003eChildhood obesity is a serious and urgent public health problem that is associated with physical and psychological comorbidities (6). The bidirectional association between obesity and FGID has been described in previous studies, however, some of them are limited by a lack of control groups or outdated diagnostic criteria (7-9), and none of them was based on ROME IV criteria. The primary aim of this study was to define the association between obesity and functional abdominal pain (FAP) disorders in children according to the Rome IV criteria compared with a population control, and to describe and compare clinical characteristics of children with overweight/obesity with those of healthy weight and FAP disorders.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAll study procedures were approved by the institutional review board of the Tel Aviv Medical Center (Helsinki Committee), and parental informed consent was obtained for all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design and Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective study of 2- to 18-year-old children with a clinical diagnosis of FAP disorders that were followed-up in the Pediatric Gastroenterology Unit at the \"Dana-Dwek\" Children's Hospital, Tel Aviv, Israel, between January 2016 and October 2018. The Pediatric Gastroenterology unit is an outpatient clinic at our hospital, which is a tertiary referral center for pediatric gastroenterology. The patients were identified through the local electronic health records database. After the patients with clinical diagnosis of FAP were identified from the medical records, we performed an objective evaluation of the compatibility of their diagnosis with the ROME IV criteria (3). Patients that did not fulfill these criteria were excluded from the study, as were patients with missing anthropometric data. Body mass index (BMI) percentiles were defined by the CDC standards (10). Patients with BMIs \u0026ge;85\u003csup\u003eth\u003c/sup\u003e percentile were designated as being overweight or obese.\u003c/p\u003e\n\u003cp\u003eA population control group was obtained from the 2015-2016 Israel national health survey (11). The Israeli health survey is a national survey, conducted every 3-4 years by the ministry of health of Israel, that aims to investigate health and nutrition status among the Israeli population by a representative sample of children and adults. The data in the survey is presented according to age groups (2-11 and 12-18 years of age) and gender. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively reviewed the patients' records and collected demographic data consisting of age, gender, location and duration of symptoms (abdominal pain, vomiting, diarrhea, heartburn) as well as anthropometric data (weight, height, BMI). We also reviewed imaging and endoscopies studies, hospitalizations, dietitian consultations, nutrition recommendations, and follow-up durations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Statistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCategorical variables were reported as frequency and percentage. Continuous variables were evaluated for normal distribution using a histogram and Kolmogorov\u0026ndash;Smirnov test. Since none of the continuous variables were normally distributed, they were reported as median and interquartile range (IQR). Overweight proportion was compared to the published data using the one-sample binomial test. Characteristics of overweight and non-overweight children were compared using the Chi-square test or Fisher's exact test for the categorical variables, and the Mann-Whitney test was used for the continuous and ordinal variables. All statistical tests were two-sided, and \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant. SPSS was used for all statistical analyses (IBM SPSS Statistics, version 25, IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographic and Clinical Data \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 274 children were identified as having the diagnosis of FAP. Forty-eight children who did not meet the ROME IV criteria and 53 children with missing data were excluded, leaving a total of 173 children for final analysis. Of these children, 114 (65.8%) were females, and the group\u0026rsquo;s median age was 11.5 (IQR 7.9-14.5) years, nearly all of them were from Israeli Jewish origin (170 patients, 98.3%). The functional disorders were functional abdominal pain NOS (\u003cem\u003en\u003c/em\u003e = 71, 41%), IBS (\u003cem\u003en\u003c/em\u003e = 67, 38.8%), and FD (\u003cem\u003en\u003c/em\u003e = 35, 20.2%). No abdominal migraine cases were identified. The median duration of the abdominal pain was 8 months (IQR 4-20), the median BMI percentile was 64 (IQR 26.7-86.5), and the median follow-up duration was 2.1 months (IQR 0-6). The demographic and clinical data are presented in Table 1.\u003c/p\u003e\n\u003cp\u003eSixty children (36.4%) underwent gastroscopy, 13 (7.5%) underwent colonoscopy, and 132 (76.3%) underwent imaging studies, of whom 115 (66.5%) had an abdominal ultrasound and 17 (9.8%) had an abdominal computerized tomography or a magnetic resonance enterography. Ninety-nine children (57.2%) received medications: 50 (28.9%) were treated with stool softeners, 38 (22%) with proton pump inhibitors (PPI), and 11 (6.4%) with probiotics. No gender difference was noticed in medication use. However, significantly more children with FD were treated with PPI compared to children with IBS and functional abdominal pain NOS (57.1%, 13.4% and 12.7%, respectively, P\u0026lt;0.001). Twenty children (11.5%) were hospitalized due to FAP. In addition, 105 children (60.6%) were given general balanced dietary recommendations from the physician and 46 (26.5%) children received formal dietitian consultations. Specific dietary recommendations were given as follows: high fiber (\u003cem\u003en\u003c/em\u003e = 38, 22%), reduced simple carbohydrates (\u003cem\u003en\u003c/em\u003e = 24, 13.9%) or lactose free (\u003cem\u003en \u003c/em\u003e= 19, 11%).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOverweight/obese vs. normal weight in FAP group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf all 173 children, 53 children (30.6%) were accounted as overweight/obese. Among these 53 children, 20 were truly obese (37.7%), 15 (28.3%) boys and 38 (71.7%) girls. The distribution of FAP disorders among the children with overweight/obesity was as follow; 22 (41.5%) with IBS, 16 (30.2%) with functional abdominal pain-NOS and 15 (28.3%) with FD (Table 1). No significant relation was found between obesity and FAP subgroups. Children with FAP and overweight/obesity disorders were older (12.4 (9.8-15.3) vs. 10.8 (7.4-14.1), p=0.04), had more hospitalizations due to FAP (20.8% vs. 7.5% p=0.01), were treated more with PPI (26.4% vs. 20%, p=0.05) and had more dietitian consultations (43.4% vs. 19.2%, p=0.001) compared with children with FAP and normal weight (Table 1). There was no significant difference in gender, endoscopies and imaging studies performance, follow up duration and nutrition recommendations between the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe FAP Group vs. the Controls \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 6432 controls were divided into two age groups, one 2-11 years of age and one 12-18 years of age. The younger age group included 1792 children, of whom 919 (51.3%) were boys and 873 (48.7%) were girls. There were 299 children (16.7%) in the young age group who were designated as having overweight/obesity. The older age group of 4640 children included 2223 (47.9%) boys and 2417 (52%) girls, among whom 1433 (30.8%) were designated as having overweight/obesity (Table 2). The 2- to 11-year-old girls with FAP had a significantly higher prevalence of overweight/obesity compared with the controls in that age range (70.6% vs. 48.7%, \u003cem\u003ep\u003c/em\u003e = 0.04) (Table 2). In addition, the 12- to 18-year old children with FAP had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30.8%, respectively, \u003cem\u003ep \u003c/em\u003e= 0.04), and specifically in girls (42.9% vs. 29.2%, \u003cem\u003ep\u003c/em\u003e = 0.01) in that age range. There was no significant difference between prevalence of overweight/obesity of boys with FAP in any age group compared to controls.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe association between obesity and FAP according to the updated ROME IV criteria had not been investigated before. In the current study, our analysis of that association revealed a higher prevalence of overweight/obesity among adolescents with FAP disorders compared to an age- and sex-matched control population. Our results are in line with studies that had demonstrated a correlation between body weight and FGID. Teitelbaum et al (8) showed a greater percentage of children with obesity and constipation, gastroesophageal reflux disease, IBS, encopresis and FAP compared with children with healthy weight. In their study, functional disorders were assigned based on ROME II criteria without specification of subtypes of FAP. From another point of view, Bonilla et al (9) described a cohort from 2007-2008 with a prevalence of 20.2% obesity in patients with FGID, however, no comparison to healthy control group was performed. They showed that obesity was associated with poor outcome and disability at long term follow up. In our study the prevalence of overweight/obesity was higher, probably attributed to the combination of children with overweight and obesity as one group or to the increase in prevalence of obesity in the western world as part of the obesity epidemic. Other studies demonstrated higher percentages of recurrent abdominal pain (12) and FGID (7) in children with obesity. However, Malaty et al (12) used a non-validated questionnaire and the latter study was based on ROME III criteria for diagnosis of functional disorders.\u003c/p\u003e\n\u003cp\u003eSeveral factors may explain the association between obesity and FAP disorders. Dietary habits are a major factor in obesity development and previous studies showed the association between increased consumption of carbohydrates and high body weight (13, 14, 15). Carbohydrate malabsorption may cause gastrointestinal symptoms via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation (16). Moreover, there is some evidence that a low-FODMAP diet is effective in reducing IBS symptoms (17, 18). Recently, Schnabel et al showed an association between ultra-processed food (UPF) consumption and functional gastrointestinal disorders.\u0026nbsp; In this large French cohort, an increase in UPF, which is characterized by high density of saturated fatty acids, sugar, sodium and low content of protective nutrients such as fibers, was associated with a higher risk of IBS. They also found that UPF consumption was associated with higher BMI. (19). In addition to dietary habits, sedentary lifestyle and lack of physical activity could be related to both obesity and functional pain (20).\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA potential association between obesity, FGID and gastrointestinal motility disorders has also been described. Delayed gastric emptying and impaired antral motility were found in children with RAP, FAP, IBS or functional dys\u0026shy;pepsia (21, 22). Several studies have shown delayed gastric emptying and gastric and gallbladder dysmotility in the individuals with obesity (23, 24). This may be attributed to increased gastric distention in the obese causing poor fundal and antral tone (25), altered sensitivity of mechanoreceptors in the stomach musculature (26) and abnormal perception of satiety signals (27). Another association between obesity and FGID is the gut microbiota. Increased risk of small intestinal bacterial overgrowth (28) and different gut microbiota composition (29) in obesity has been reported which might contribute to gastrointestinal dysmotility, excessive fermentation, altered visceral perception and gut permeability with their metabolites leading to pain-predominant FGID (30, 31). Finally, obesity and FGID share common psychological comorbidities, such as stress, depression, and anxiety, which can contribute to each other's development and aggravate each other (32,33,34). \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe higher prevalence of overweight/obesity in females with FAP compared to controls may be attributed to several factors. Females are more prone to several gastrointestinal motility disorders, such as delayed gastric emptying, compared to males (35,36). It has been suggested that this difference may be caused by female ovarian hormones. Gender differences in intestinal microbiome in addition to microbiome difference between children with overweight/obesity and children with healthy weight (37) may serve as an alternative explanation.\u0026nbsp; Our study has demonstrated a few significant differences between children with FAP having overweight/obesity compared to normal weight children. We found that children with overweight/obesity had more hospitalizations attributed to their abdominal pain compared with children with healthy weight, as described in other studies which suggested that pediatric obesity contributes significantly to increased health care utilization in children (38, 39). A possible explanation to increased health care utilization in children with obesity is comorbidities of obesity (38). In addition, children with obesity might be more symptomatic compared to children with normal weight (40). We also found that obese children with FAP are treated more frequently with PPI than non-obese children with FAP. Parkman et al (36) reported that patients with obesity and idiopathic gastroparesis tend to be more symptomatic compared to patients with healthy weight. Whether this is true to patients with FAP is to be elucidated. Although no relation between FAP subgroups and obesity was established in this study, children with FD were treated more frequently with PPI, in line with the ROME IV recommendations (3), compared to other FAP subgroups. Generally, overuse of PPI has been increasing in the last decade in hospitalized and ambulatory patients and their prescription continues to grow in all western countries (41). \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe clinical implications of the findings of our current study relate to the management of children with overweight/obesity and FGID. Although this study could not indicate causality between obesity and FAP, the findings support a relation between these conditions. The treatment protocol of children with obesity and FAP should also focus on guidance for more thorough nutritional assessment targeted towards weight reduction together with other lifestyle changes (e.g., increase in physical activities) that may improve symptoms and prevent or at least minimize the need for medications and hospitalizations.\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this is the first study to show an association between obesity and FAP diagnosed in children according to the updated ROME IV criteria for diagnosis of FAP, which was made by a pediatric gastroenterologist in a clinic setting and not by collecting information from a self-administered questionnaire. This study is limited by its retrospective nature, missing more precise data on skinfold measurements, body composition, and other parameters. In addition, our control group might include children with FAP disorders, although we believe that due to the high number of children included, the percentage of children with FAP disorders would be similar to the general population. Lastly, a part of children with diagnosis of FAP in the medical records did not fulfil the ROME IV criteria and therefore were excluded. In real life, some degree of incompatibility between clinical diagnosis and formal criteria may be anticipated. Another explanation is the difference between ROME IV and ROME III criteria, that was one of the rationales to conduct the current study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAdolescents with FAP disorders have a higher prevalence of overweight/obesity compared with controls in the general population. Children with FAP and overweight/obesity have more hospitalizations and medical treatment with PPI compared to children with FAP disorders who are of normal weight. Heightened awareness of these findings might improve treatment planning and management to meet the needs of children with overweight/obesity and FAP. Further studies should focus on the interrelationship between FGID and obesity and specifically on the pathophysiologic mechanisms between these conditions, and also to investigate the effect of weight reduction on FAP symptoms. \u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFGID\u003cstrong\u003e-\u003c/strong\u003e Functional gastrointestinal disorders\u003c/p\u003e\n\u003cp\u003eFD- functional dyspepsia\u003c/p\u003e\n\u003cp\u003eIBS- irritable bowel syndrome\u003c/p\u003e\n\u003cp\u003eNOS- not otherwise specified\u003c/p\u003e\n\u003cp\u003eFAP- functional abdominal pain\u003c/p\u003e\n\u003cp\u003eBMI- Body mass index\u003c/p\u003e\n\u003cp\u003eIQR- interquartile range\u003c/p\u003e\n\u003cp\u003ePPI- proton pump inhibitors\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll study procedures were approved by the institutional review board of the Tel Aviv Medical Center (Helsinki Committee), and written parental informed consent was obtained for all participants.( 0402-14-TLV)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Not applicable\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAvailability of data and materials\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\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\u003cu\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthors' contributions\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTG, HML and AYF formulated the research question and designed the study. TG, ABT, YW, AA analyzed the data, and wrote the manuscript. OS, AA, YW collected the data. DL is the registered dietitian in this study; SC supervised the statistical analysis, and revised the manuscript.\u003cstrong\u003e\u003cu\u003e All authors\u003c/u\u003e\u003c/strong\u003e critically reviewed the manuscript and approved the final version submitted for publication\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAcknowledgements\u003c/u\u003e: \u003c/strong\u003eNot Applicable\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eShort title\u003c/strong\u003e:\u003c/span\u003e Obesity in children with functional abdominal pain\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003eTransparency declaration:\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eThe lead author affirms that this manuscript is an honest, accurate and transparent account of the study being reported.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRouster AS, Karpinski AC, Silver D, et al. Functional gastrointestinal disorders dominate pediatric gastroenterology outpatient practice. \u003cem\u003eJ Pediatr Gastroenterol Nutr\u003c/em\u003e 2016;62:847-851.\u003c/li\u003e\n\u003cli\u003eKorterink J, Devanarayana NM, Rajindrajith S, et al. Childhood functional abdominal pain: mechanisms and management. \u003cem\u003eNat Rev Gastroenterol Hepatol\u003c/em\u003e 2015;12:159-171.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Rasquin%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=16678566\"\u003eRasquin A\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Di%20Lorenzo%20C%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=16678566\"\u003eDi Lorenzo C\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Forbes%20D%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=16678566\"\u003eForbes D\u003c/a\u003e, et al. Childhood functional gastrointestinal disorders: child/adolescent. \u003cem\u003eGastroenterology\u003c/em\u003e 2016;150:1456-1468.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Devanarayana%20NM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25059210\"\u003eDevanarayana NM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Rajindrajith%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25059210\"\u003eRajindrajith S\u003c/a\u003e, Perera MS, et al. Association between functional gastrointestinal diseases and exposure to abuse in teenagers. \u003cem\u003eJ Trop Pediatr\u003c/em\u003e 2014;60:386-392.\u003c/li\u003e\n\u003cli\u003eSaps M, Velasco-Benitez CA, Langshaw AH, et al. Prevalence of functional gastrointestinal disorders in children and adolescents: comparison between Rome III and Rome IV criteria. \u003cem\u003eJ Pediatr\u003c/em\u003e 2018;199:212-216.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Sanders%20RH%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25922141\"\u003eSanders RH\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Han%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25922141\"\u003eHan A\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Baker%20JS%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25922141\"\u003eBaker JS\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Cobley%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25922141\"\u003eet\u003c/a\u003e al. Childhood obesity and its physical and psychological co-morbidities: a systematic review of Australian children and adolescents. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=childhood+obesity+and+its+physical+and+psychological+comorbidities%3A+a+systematic+review+of+Australian+children+and+adolescents.\"\u003e\u003cem\u003eEur J Pediatr\u003c/em\u003e\u003c/a\u003e 2015; 174:715-746.\u003c/li\u003e\n\u003cli\u003eTambucci R, Quitadamo P, Ambrosi M, et al. Association between obesity/overweight and functional gastrointestinal disorders in children. \u003cem\u003eJ Pediatr Gastroenterol Nutr\u003c/em\u003e\u0026nbsp; 2019; 68:517-520.\u003c/li\u003e\n\u003cli\u003eTeitelbaum JE, Sinha P, Micale M, et al. Obesity is related to multiple functional abdominal diseases. \u003cem\u003eJ Pediatr\u003c/em\u003e 2009; 154:444-446.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Bonilla%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21079618\"\u003eBonilla S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20D%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21079618\"\u003eWang D\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Saps%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21079618\"\u003eSaps M\u003c/a\u003e. Obesity predicts persistence of pain in children with functional gastrointestinal disorders. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Obesity+predicts+persistence+of+pain+in+children+with+functional+gastrointestinal+disorders\"\u003e\u003cem\u003eInt J Obes (Lond)\u003c/em\u003e\u003c/a\u003e \u0026nbsp;2011; 35:517-521.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.cdc.gov/growthcharts/clinical_charts.htm\"\u003ehttps://www.cdc.gov/growthcharts/clinical_charts.htm\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003ehttps://www.health.gov.il/UnitsOffice/ICDC/mabat/Pages/default.aspx\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Malaty%20HM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17391473\"\u003eMalaty HM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Abudayyeh%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17391473\"\u003eAbudayyeh S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Fraley%20K%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17391473\"\u003eFraley K\u003c/a\u003e, et al. Recurrent abdominal pain in school children: effect of obesity and diet. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Recurrent+abdominal+pain+in+school+children%3A+effect+of+obesity+and+diet.\"\u003e\u003cem\u003eActa Paediatr\u003c/em\u003e\u003c/a\u003e 2007; 96:572-576.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Emmett%20PM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=26395342\"\u003eEmmett PM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Jones%20LR%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=26395342\"\u003eJones LR\u003c/a\u003e. Diet, growth, and obesity development throughout childhood in the Avon Longitudinal Study of Parents and Children. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Diet%2C+growth%2C+and+obesity+development+throughout+childhood+in+the+Avon+Longitudinal+Study+of+Parents+and+Children\"\u003e\u003cem\u003eNutr Rev\u003c/em\u003e\u003c/a\u003e 2015; 73:175-206.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Te%20Morenga%20L%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23321486\"\u003eTe Morenga L\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Mallard%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23321486\"\u003eMallard S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Mann%20J%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23321486\"\u003eMann J\u003c/a\u003e. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/23321486\"\u003e\u003cem\u003eBMJ\u003c/em\u003e\u003c/a\u003e 2012 15; 346: e7492.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Dello%20Russo%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30248889\"\u003eDello Russo M\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Ahrens%20W%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30248889\"\u003eAhrens W\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=De%20Henauw%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30248889\"\u003eDe Henauw S\u003c/a\u003e, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=IDEFICS%20Consortium%5BCorporate%20Author%5D\"\u003eIDEFICS Consortium\u003c/a\u003e. The Impact of Adding Sugars to Milk and Fruit on Adiposity and Diet Quality in Children: A Cross-Sectional and Longitudinal Analysis of the Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) Study. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=The+Impact+of+Adding+Sugars+to+Milk+and+Fruit+on+Adiposity+and+Diet+Quality+in+Children%3A+A+Cross-Sectional+and+Longitudinal+Analysis+of+the+Identification+and+Prevention+of+Dietary-+and+Lifestyle-Induced+Health+Effects+in+Children+and+Infants+(IDEFICS)+Study\"\u003e\u003cem\u003eNutrients\u003c/em\u003e.\u003c/a\u003e 2018; 21;10:1350.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Chumpitazi%20BP%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27355647\"\u003eChumpitazi BP\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Shulman%20RJ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27355647\"\u003eShulman RJ\u003c/a\u003e. Dietary Carbohydrates and Childhood Functional Abdominal Pain. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/27355647\"\u003e\u003cem\u003eAnn Nutr Metab\u003c/em\u003e\u003c/a\u003e 2016; 68:8-17.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Shepherd%20SJ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23588241\"\u003eShepherd SJ\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Lomer%20MC%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23588241\"\u003eLomer MC\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Gibson%20PR%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23588241\"\u003eGibson PR\u003c/a\u003e. Short-chain carbohydrates and functional gastrointestinal disorders. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/23588241\"\u003e\u003cem\u003eAm J Gastroenterol\u003c/em\u003e\u003c/a\u003e 2013; 108:707-17.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Staudacher%20HM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21615553\"\u003eStaudacher HM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Whelan%20K%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21615553\"\u003eWhelan K\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Irving%20PM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21615553\"\u003eIrving PM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Lomer%20MC%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=21615553\"\u003eet\u003c/a\u003e Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Comparison+of+symptoms+response+following+advice+for+a+diet+low+in+fermentable+carbohydrates+(FODMAP)+versus+standard+dietary+advice+in+patients+with+irritable+bowel+syndrome\"\u003e\u003cem\u003eJ Hum Nutr Diet\u003c/em\u003e\u003c/a\u003e 2011; 24:487-495.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Schnabel%20L%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=29904158\"\u003eSchnabel L\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Buscail%20C%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=29904158\"\u003eBuscail C\u003c/a\u003e , \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Sabate%20JM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=29904158\"\u003eSabate JM\u003c/a\u003e, et al. Association Between Ultra-Processed Food Consumption and Functional Gastrointestinal Disorders: Results From the French NutriNet-Sant\u0026eacute; Cohort. \u003cem\u003eJPGN\u003c/em\u003e 2013; 57: 141\u0026ndash;148.\u003c/li\u003e\n\u003cli\u003eRabbitts JA, Holley AL, Karlson CW, Palermo TM. Bidirectional associations between pain and physical activity in adolescents. \u003cem\u003eClin J Pain\u003c/em\u003e 2014;30:251\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Devanarayana%20NM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23201712\"\u003eDevanarayana NM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Rajindrajith%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23201712\"\u003eRajindrajith S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Bandara%20C%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23201712\"\u003eBandara C\u003c/a\u003e, et al. Ultrasonographic assessment of liquid gastric emptying and antral motility according to the subtypes of irritable bowel syndrome in children. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=A.+Ultrasonographic+assessment+of+liquid+gastric+emptying+and+antral+motility+according+to+the+subtypes+of+irritable+bowel+syndrome+in+children.\"\u003e\u003cem\u003eJ Pediatr Gastroenterol Nutr\u003c/em\u003e\u003c/a\u003e 2013; 56(4):443-448.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Devanarayana%20NM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23517336\"\u003eDevanarayana NM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Rajindrajith%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23517336\"\u003eRajindrajith S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Perera%20MS%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=23517336\"\u003ePerera MS\u003c/a\u003e, et al. Gastric emptying and antral motility parameters in children with functional dyspepsia: association with symptom severity. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Gastric+emptying+and+antral+motility+parameters+in+children+with+functional+dyspepsia%3A+association+with+symptom+severity\"\u003e\u003cem\u003eJ Gastroenterol Hepatol\u003c/em\u003e\u003c/a\u003e 2013; 28:1161-1166.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Di%20Ciaula%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=22497555\"\u003eDi Ciaula A\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20DQ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=22497555\"\u003eWang DQ\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Portincasa%20P%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=22497555\"\u003ePortincasa P\u003c/a\u003e. Gallbladder and gastric motility in obese newborns, pre-adolescents and adults. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Gallbladder+and+gastric+motility+in+obese+newborn%2C+pre-adolescents+and+adults.++Gastroenterology\"\u003eJ\u003cem\u003e Gastroenterol Hepatol\u003c/em\u003e\u003c/a\u003e 2012; 27:1298-1305.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Jackson%20SJ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=15171750\"\u003eJackson SJ\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Leahy%20FE%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=15171750\"\u003eLeahy FE\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=McGowan%20AA%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=15171750\"\u003eMcGowan AA\u003c/a\u003e, et al. Delayed gastric emptying in the obese: an assessment using the non-invasive (13) C-octanoic acid breath test. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Delayed+gastric+emptying+in+the+obese%3A+an+assessment+using+the+non-invasive+C-octanoic+acid+breath+test.\"\u003e\u003cem\u003eDiabetes Obes Metab\u003c/em\u003e\u003c/a\u003e 2004; 6:264-270.\u003c/li\u003e\n\u003cli\u003eHorowitz M, Collins PJ, Cook DJ et al. Abnormalities of gastric emptying in obese patients. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/6642853\"\u003e\u003cem\u003eInt J Obes.\u003c/em\u003e\u003c/a\u003e 1983;7:415-421.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Maddox%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2762759\"\u003eMaddox A\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Horowitz%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2762759\"\u003eHorowitz M\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Wishart%20J%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2762759\"\u003eWishart J\u003c/a\u003e, et al. Gastric and oesophageal emptying in obesity. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/2762759\"\u003e\u003cem\u003eScand J Gastroenterol\u003c/em\u003e\u003c/a\u003e 1989; 24:593-598.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Horowitz%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=3957711\"\u003eHorowitz M\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Collins%20PJ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=3957711\"\u003eCollins PJ\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Shearman%20DJ%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=3957711\"\u003eShearman DJ\u003c/a\u003e. Effect of increasing the caloric/osmotic content of the liquid component of a mixed solid and liquid meal on gastric emptying in obese subjects. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=.+Effect+of+increasing+the+caloric%2Fosmotic+content+of+the+liquid+component+of+a+mixed+solid+and+liquid+meal+on+gastric+emptying+in+obese+subjects\"\u003e\u003cem\u003eHum Nutr Clin Nutr\u003c/em\u003e\u003c/a\u003e1986; 40:51-56.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Roland%20BC%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=28940740\"\u003eRoland BC\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Lee%20D%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=28940740\"\u003eLee D\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Miller%20LS%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=28940740\"\u003eMiller LS\u003c/a\u003e,\u0026nbsp;et al. Obesity increases the risk of small intestinal bacterial overgrowth (SIBO). \u003cem\u003eNeurogastroenterology\u0026amp;Motility\u003c/em\u003e 2018;3:e13199.\u003c/li\u003e\n\u003cli\u003eHou YP, He QQ, Ouyang HM, et al. Human Gut Microbiota Associated with Obesity in Chinese Children and Adolescents. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/29214176\"\u003e\u003cem\u003eBiomed Res Int.\u003c/em\u003e\u003c/a\u003e2017; 758598.\u003c/li\u003e\n\u003cli\u003eRhee, S. H., Pothoulakis, C. \u0026amp; Mayer, E. A. Principles and clinical implications of the brain\u0026ndash;gut\u0026ndash;enteric microbiota axis. \u003cem\u003e Rev. Gastroenterol. Hepatol.\u003c/em\u003e 2009; 6:306\u0026ndash;314\u003c/li\u003e\n\u003cli\u003eOhman, L. \u0026amp; Simren, M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). \u003cem\u003eCurr Gastroenterol Rep\u003c/em\u003e 2013; 15: 323.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Top%C3%A7u%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=26565543\"\u003eTop\u0026ccedil;u S\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Orhon%20F%C5%9E%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=26565543\"\u003eOrhon FŞ\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Tayfun%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=26565543\"\u003eTayfun M\u003c/a\u003e,\u0026nbsp;et al. Anxiety, depression and self-esteem levels in obese children: a case-control study. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/26565543\"\u003e\u003cem\u003eJ Pediatr Endocrinol Metab\u003c/em\u003e\u003c/a\u003e 2016; 29:357-361.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Shin%20NY%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=18346504\"\u003eShin NY\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Shin%20MS%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=18346504\"\u003eShin MS\u003c/a\u003e. Body dissatisfaction, self-esteem, and depression in obese Korean children. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Body+dissatisfaction%2C+self-esteem%2C+and+depression+in+obese+Korean+children\"\u003e\u003cem\u003eJ Pediatr\u003c/em\u003e\u003c/a\u003e2008;152: 502-506.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Campo%20JV%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=19476302\"\u003eCampoJV\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Gilchrist%20RH%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=19476302\"\u003eGilchrist RH\u003c/a\u003e. Psychiatric comorbidity and functional abdominal pain. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/19476302\"\u003e\u003cem\u003ePediatr Ann\u003c/em\u003e\u003c/a\u003e 2009; 38:283-287.\u003c/li\u003e\n\u003cli\u003eZia JK, Heitkemper MM. Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease. \u003cem\u003eGastroenterol Clin North Am\u003c/em\u003e. 2016;45(2):239-51.\u003c/li\u003e\n\u003cli\u003eParkman HP, Yates K, Hasler WL et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. \u003cem\u003eGastroenterology\u003c/em\u003e 2011;140(1):101-15.\u003c/li\u003e\n\u003cli\u003eGao X, Jia R, Xie L et al. A study of the correlation between obesity and intestinal flora in school-age children. \u003cem\u003eSci Rep\u003c/em\u003e 2018;8(1):14511.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Hampl%20SE%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17199061\"\u003eHampl SE\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Carroll%20CA%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17199061\"\u003eCarroll CA\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Simon%20SD%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17199061\"\u003eSimon SD\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Sharma%20V%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=17199061\"\u003eet\u003c/a\u003e al. Resource utilization and expenditures for overweight and obese children. \u003cem\u003eArch Pediatr Adolesc Med\u003c/em\u003e. 2007; 161:11-14.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Trasande%20L%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=19300433\"\u003eTrasande L\u003c/a\u003e,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Chatterjee%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=19300433\"\u003eChatterjee S\u003c/a\u003e. The impact of obesity on health service utilization and costs in childhood. \u003cem\u003eObesity\u003c/em\u003e.2009; 17:1749-1754.\u003c/li\u003e\n\u003cli\u003eGrout RW, Thompson-Fleming R, Carroll AE, et al. Prevalence of pain reports in pediatric primary care and association with demographics, body mass index, and exam findings: a cross-sectional study. \u003cem\u003eBMC Pediatr\u003c/em\u003e 2018;18(1):363.\u003c/li\u003e\n\u003cli\u003e\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Lanas%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27166129\"\u003eLanas A\u003c/a\u003e. We Are Using Too Many PPIs, and We Need to Stop: A European Perspective. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=We+Are+Using+Too+Many+PPIs%2C+and+We+Need+to+Stop%3A+A+European+Perspective.\"\u003e\u003cem\u003eAm J Gastroenterol\u003c/em\u003e\u003c/a\u003e2016; 111:1085-1086.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\"\u003eTable 1. Demographic and clinical data\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"float: left;border-collapse:collapse;border:none;margin-left:6.75pt;margin-right:6.75pt;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border: 1pt solid windowtext;padding: 0in 5.4pt;height: 63.3pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 63.3pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eStudy cohort\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=173\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 63.3pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eNormal or underweight\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=120 (69.3%)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 63.3pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eOverweight or obese\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=53 (30.7%)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 63.3pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eAge (years)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e11.5 (7.9-14.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e10.8 (7.4-14.1)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e12.4 (9.8-15.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.04\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFemales\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e114 (65.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e76 (63.3%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e38 (71.7%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 84.8pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFAP disorders:\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFunctional abdominal pain NOS\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eIrritable bowel syndrome\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFunctional dyspepsia\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.8pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e71 (41%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e67 (38.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e35 (20.2%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.8pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e55 (45.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e45 (37.5%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e20 (16.7%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.8pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e16 (30.2%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e22 (41.5%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e15 (28.3%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 84.8pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.07\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eHospitalizations\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e20 (11.6%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u0026nbsp;9 (7.5%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e11 (20.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.01\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eProton pump inhibitors treatment\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e38 (22%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e24 (20%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e14 (26.4%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.05\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113.15pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eDietitian consultations\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e46 (26.6%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e23 (19.2%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e23 (43.4%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 24.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-size: 12px; color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:8.0pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;line-height:107%;'\u003e\u003cbr\u003e\u003c/p\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\n\u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;line-height:200%;'\u003e\u003cspan style=\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\"\u003eTable 2. Overweight Patients in the FAP and Control Groups by Age and Gender\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"right\" dir=\"rtl\" style='margin:0in;margin-bottom:.0001pt;text-align:right;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\n \u003ctable dir=\"rtl\" style=\"float: left;border-collapse:collapse;border:none;margin-left:6.75pt;margin-right:6.75pt;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=4640\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eFAP group\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=81\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eChildren 12-18 years old\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.04\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e1433 (30.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e32 (39.5%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eTotal overweight/obese\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.44\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e2223 (47.9%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e726 (32.6%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e32 (39.5%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e11 (34.4%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eMales\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eOverweight/obese males\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.01\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e2417 (52%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e707 (29.2%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e49 (60.4%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e21 (42.9%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFemales\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eOverweight/obese females\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eControl N=1792\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eFAP group\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eN=92\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e\u003cstrong\u003eChildren 2-11 years old\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.07\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e299 (16.7%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e21 (22.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eTotal overweight/obese\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.5\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e919 (51.3%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e148 (16.1%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e27 (29.3%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e4 (14.8%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eMales\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eOverweight/obese males\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 50.75pt;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-left: 1pt solid windowtext;border-image: initial;border-top: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e0.04\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e873 (48.7%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e151 (17.3%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e65 (70.6%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003e17 (26.2%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169.8pt;border-top: none;border-left: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eFemales\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-size: 12px;\"\u003e\u003cspan style=\"font-family: Helvetica;\"\u003eOverweight/obese females\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\" style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u003cspan style=\"font-family: Helvetica; font-size: 12px; color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\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":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"functional gastrointestinal disorders; children; irritable bowel syndrome; overweight; obesity.","lastPublishedDoi":"10.21203/rs.2.20433/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.20433/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a retrospective study of children\u003cstrong\u003e \u003c/strong\u003e(2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85\u003csup\u003eth\u003c/sup\u003e percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. \u003c/p\u003e\u003cp\u003eAdolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, \u003cem\u003ep \u003c/em\u003e= 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, \u003cem\u003ep \u003c/em\u003e= 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, \u003cem\u003ep \u003c/em\u003e= 0.01) compared to Children with FAP and normal weight. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-05-13 14:16:04","doi":"10.21203/rs.2.20433/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-04-28T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-04-27T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-04-26T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-01-06T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-03-24 17:08:07","doi":"10.21203/rs.2.20433/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-04-23T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-03-31T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-03-31T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-03-31T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nThe responses by the authors are sufficient, and I recommend this manuscript for publication. Congratulations to the study team.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-03-31T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-03-31T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nI believe that the authors have responded to the majority of the suggestions of the reviewers. There are still several areas in which person-first language (i.e., patient/population with obesity vs. obese patient/population) needs to be applied, including but not limited to p. 3 line 24, p. 6 line 22, p. 8 line 1 and p. 9 line 21.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"editorAssigned","content":"","date":"2020-03-19T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-18T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-18T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-01-09 19:35:08","doi":"10.21203/rs.2.20433/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-02-25T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-02-24T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nThis is an interesting manuscript discussing the differences in prevalence of FAP in children with overweight/obesity vs. those with healthy weight. The study consisted of children seen in a tertiary care GI clinic and the control group were healthy children from the Israel national health survey from the beginning of the study period. The manuscript represents a good first step in understanding the association between overweight/obesity and FAP according to the newest Rome criteria, and could be improved with some revisions and an expanded discussion section. Specific comments by section follow.\nAbstract and body of manuscript: The American Academy of Pediatrics, The Obesity Society and other national organizations now recommend the use of person-first language when writing about or discussing children or adults with obesity. This practice avoids labeling the patient or defining the patient by their disease. The same could be said for the term \"FAP children\". So throughout the manuscript, it would be preferred to use statements such as, \"Children with FAP and overweight/obesity\" vs. \"Overweight FAP children\"; \"...having overweight/obesity\" vs. \"being overweight/obese\"; \"Children with overweight/obesity and children with healthy weight...\" vs. \"...overweight and non-overweight children...\". Also, the spelling of dietitian needs to be corrected throughout.\nBackground and Methods: No other comments\nResults: Section 3.1: Under demographic data, is it correct to assume that children's race/ethnicity were all the same, or were these variables not examined? Section 3.3, p. 6, line 56: Minor point, but for consistency with statements earlier in this paragraph, it might be better to list the findings in younger children with FAP before older children. On p. 7 line 5, the percentages appear to be flipped. The last sentence of this paragraph is awkward, and could be reworded with something like, \"There was no significant difference between prevalence of overweight/obesity in boys with FAP vs. boys with healthy weight in any age group.\"\nSection 3.2 p. 6 line 36: Should use \"nutrition\" vs. \"nutritious\".\nDiscussion: This section would benefit from expansion on 1) possible reasons why girls in both age groups are driving the association between obesity and FAP. The authors mention associations or potential associations between obesity and several factors that may lead to FAP. Are any of these conditions (ex. motility disorders, gut microbiota abnormalities) more common in girls vs. boys? 2) any clinical implications; and 3) further research directions. A few other specific areas for further expansion include p. 9 line 1--more hospitalizations for children with obesity and FAP--ideas on why?; line 7--thoughts on why girls with obesity and FAP are more commonly treated with PPIs vs. boys? and p. 9 line 17--Who are the authors referring to when they state, \"They advocate that the treatment protocol...\" The findings? If so, maybe a word like \"support\" would be more appropriate."},{"type":"editorInvitedReview","content":"","date":"2020-02-06T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nThank you for the opportunity to review this manuscript. The authors present a retrospective review of children with FAP in a peds GI clinic, and test the rates of obesity within that population. In addition, they compare obesity rates to a population control from a national survey. The scientific question is justified given new Rome IV criteria. However, the methods have are either inadequately described or are flawed, and the analysis and conclusion needs more depth. The conclusions need to be clarified to be in line with the results of the study.\n\nAbstract\n- Technical note: The BMI unit used here is percentile, not percent. This comment applies throughout the manuscript.\n\nBackground\n- Clarify if day-to-day practice is peds GI or general peds.\n- The abdominal pain NOS diagnosis is officially \"functional abdominal pain - not otherwise specified.\" The word \"functional\" is ommitted in several instances in the manuscript.\n- Prior studies also varied in their approach to the association. One looked at obese children, then determined FAP rates. Another looked at FAP children, then determined obesity rates. This is a notable difference.\n- The result of the primary aim looking at subgroups of FAP disorders is lacking. Rather, the manuscript (methods and results) seems to focus on FAP broadly.\n- The comparison with the general population isn't adressed in the aims described here, but is a significant part of the manuscript. Please reconcile.\n\nMethods\n- please clarify if the GI unit is an outpatient clinic at a hospital\n- Describe the national health survey for those not familiar with it. Is it considered representative?\n- Regarding the control group, how do you know they were healthy? I think the survey is better described as a population control. (This should be corrected throughout the manuscript.)\n- Line 27: The sentence about exclusion seems to apply to the cases, not controls, and should be placed earlier.\n- Line 29: clarify if removed people without any data or just missing at least one piece of data.\n- Was normality only assessed visually by histogram, or was a normality test done?\n\nResults\n- There appears to be an issue with the clinical diagnosis of FAP, since ~18% were not truly FAP by Rome IV criteria. I'm concerned about the bias in starting with patients with a clinical diagnosis of FAP, then. How many patients meet Rome IV criteria for FAP but are not clinical diagnosed? That set of patients doesn't appear to be included here. This issue can also be described more. It is an interesting result - comparing clinical diagnosis with actual Rome IV criteria review.\n- I recommend explicitly stating if there were no abdominal migraine diagnoses.\n- Please provide a Table 1 describing your population. The current Table 1 can be a Table 2 to describe results.\n- So 86% of patients that received dietary advice were not told to have a balanced diet? How does that improve the obesity issue?\n- 3.2, line 14: This sentence is confusing; the denominators are unclear.\n- line 17: \"The distribution of FAP disorders among the overweight/obese children was: ...\"\n- line 31: I recommend following the AAP Pediatrics journal style: \"Trend\"\n\"Use the word trend when describing a test for trend or dose-response.\nAvoid the term \"trend\" when referring to p-values near but not below 0.05. In such instances, simply report a difference and the confidence interval of the difference (if appropriate) with or without the p-value.\" The result for IBS diganosis was not significant. Additionally, this seems to be the only result addressing a primary aim looking at subgroups of FAP.\n- 3.3: Why were age and sex the two variables used to split these groups? Please justify\n- line 44: Why this breakdown in age? Please justify in the methods. Without a sound scientific reason, I am suspicious of \"p-hacking.\"\n\nDiscussion\n- Why do you think your overweight/obesity prevalence is so much higher? Because of different classification? Because you included overweight and obese? Other reasons?\n- line 42: With the word \"this\" do you mean Bonilla's study or this manuscript's work?\n- line 47: Which is the \"first\" study?\n- page 8, line 31: \"in the obese\"\n- page 9, line 7: This seems too general of a conclusion. Shouldn't this be broken down more by type of FAP? Would functional dyspepsia be more likely to be treated with PPI than other FAP? The Rome IV paper suggests PPI as a treatement.\n- page 9, line 34: Was the pediatric gastroenterologist also involved in this study? Were they aware of this study while making the diagnoses? That can be a limitation related to blinding. Additionally, related to a comment before, the diagnostic method did not appear to follow Rome IV criteria.\npage 9, line 54: This conclusion is incorrect. Only children/adolescents 12-18 meet this criteria, and again, it is compared to general population, not healthy controls."},{"type":"reviewerAgreed","content":"","date":"2020-01-31T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-01-23T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-01-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-12-30T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-12-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-12-29T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-12-27T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4e5f26a2-cca1-4996-a6cb-1dfd26ee848d","owner":[],"postedDate":"May 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":99489,"name":"Pediatrics"},{"id":99490,"name":"Gastroenterology \u0026 Hepatology"}],"tags":[],"updatedAt":"2021-07-22T20:33:40+00:00","versionOfRecord":{"articleIdentity":"rs-11040","link":"https://doi.org/10.1186/s12887-020-02106-9","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2020-05-06 20:33:40","publishedOnDateReadable":"May 6th, 2020"},"versionCreatedAt":"2020-05-13 14:16:04","video":"","vorDoi":"10.1186/s12887-020-02106-9","vorDoiUrl":"https://doi.org/10.1186/s12887-020-02106-9","workflowStages":[]},"version":"v3","identity":"rs-11040","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-11040","version":["v3"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}