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Intestinal Symptoms among Children Aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China

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Title: Intestinal Symptoms among Children Aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China
Language: English
Authors: Ting Yang, Qian Zhang, Li Chen, Ying Dai, Fei-Yong Jia, Yan Hao, Ling Li, Jie Zhang, Li-Jie Wu, Xiao-Yan Ke, Ming-Ji Yi, Qi Hong, Jin-Jin Chen, Shuan-Feng Fang, Yi-Chao Wang, Qi Wang, Chun-Hua Jin, Jie Chen, Ting-Yu Li (ORCID 0000-0002-1940-7076)
Source: Journal of Autism and Developmental Disorders. 2024 54(11):4302-4310.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 9
Publication Date: 2024
Document Type: Journal Articles
Reports - Research
Descriptors: Autism Spectrum Disorders, Symptoms (Individual Disorders), Young Children, Physical Health, Comorbidity, Foreign Countries, Human Body
Geographic Terms: China
Assessment and Survey Identifiers: Childhood Autism Rating Scale, Social Responsiveness Scale
DOI: 10.1007/s10803-023-06122-3
ISSN: 0162-3257
1573-3432
Abstract: Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.
Abstractor: As Provided
Entry Date: 2024
Accession Number: EJ1442747
Database: ERIC
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  Value: <anid>AN0180153909;aut01nov.24;2024Oct10.05:57;v2.2.500</anid> <title id="AN0180153909-1">Intestinal Symptoms Among Children aged 2–7 Years with Autism Spectrum Disorder in 13 Cities of China </title> <p>Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.</p> <p>Keywords: Autism spectrum disorder; Intestinal symptoms; Symptom score</p> <p>Copyright comment Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</p> <hd id="AN0180153909-2">Introduction</hd> <p>Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction along with the presence of restricted and repetitive patterns of behavior and interests (Lord et al., [<reflink idref="bib15" id="ref1">15</reflink>]). It is one of the most rapidly increasing serious diseases globally. The latest research from the United States Centers for Disease Control and Prevention reported that the prevalence of ASD in children aged 8 years was as high as 27.6 per 1,000 (1 in 36), indicating a significant upward trend (Maenner et al., [<reflink idref="bib18" id="ref2">18</reflink>]). In 2019, a survey of 125,806 children from eight major cities in China found that the prevalence of ASD in children aged 6–12 years was about 0.7%, with prevalence in boys being 4–5 times higher than in girls (Zhou et al., [<reflink idref="bib27" id="ref3">27</reflink>]).</p> <p>ASD is a complex neurodevelopmental disorder caused by the interaction of genetic and environmental factors. Its pathogenesis is complex and highly heterogeneous (Cheroni, Caporale, & Testa, [<reflink idref="bib5" id="ref4">5</reflink>]). Besides the aforementioned core symptoms, ASD is often accompanied by numerous other diseases, including intellectual disability, language delay, attention-deficit/hyperactivity disorder, intestinal symptoms, sleep abnormalities, and so forth. (Al-Beltagi, [<reflink idref="bib1" id="ref5">1</reflink>]; Feroe et al., [<reflink idref="bib7" id="ref6">7</reflink>]). It has been reported that the prevalence of gastrointestinal symptoms in children with ASD is about 46-84% (Al-Beltagi, [<reflink idref="bib1" id="ref7">1</reflink>]), making it one of the most common comorbidities in children with ASD (Kohane et al., [<reflink idref="bib11" id="ref8">11</reflink>]). Intestinal symptoms in children with ASD may affect other systemic symptoms, and a strong correlation is observed between them and core symptoms or other comorbidities. A previous study involving 328 children with ASD in Chongqing found that the prevalence of intestinal symptoms was significantly higher in children with autism than in the control group (Jiang et al., [<reflink idref="bib10" id="ref9">10</reflink>]). Furthermore, children with ASD with intestinal symptoms had more serious repetitive and stereotypical behaviors, problematic behaviors, and emotional symptoms (Jiang et al., [<reflink idref="bib10" id="ref10">10</reflink>]). Many children with ASD cannot verbally express pain or discomfort in a manner similar to their peers. Their inability to effectively express their symptoms and feelings often results in self-harm or unexplained emotional/behavioral outbursts (Horvath, Papadimitriou, Rabsztyn, Drachenberg, & Tildon, [<reflink idref="bib9" id="ref11">9</reflink>]). Therefore, paying attention to intestinal symptoms in children with ASD is of crucial for a comprehensive intervention of ASD.</p> <p>Unfortunately, the current clinical practice guidelines and rehabilitation training institutions in China do not routinely address potential intestinal symptoms in children with ASD. Furthermore, large-sample multicenter epidemiological data regarding the prevalence of intestinal symptoms in children with ASD are scarce. All these factors complicate the managing, diagnosing, and treating of children with ASD. Therefore, a large-scale epidemiological survey on intestinal symptoms in children with ASD in China is particularly needed. Thus, this study aimed to investigate if the presence of intestinal symptoms correlated with exacerbated ASD core symptoms.</p> <hd id="AN0180153909-3">Methods</hd> <p></p> <hd id="AN0180153909-4">Study Participants</hd> <p>Between May 2018 to December 2019, we recruited 1,222 ASD children, aged 2–7 years, from 13 locations in five geographical regions of China: the North (Harbin, Qingdao, and Changchun), East (Shanghai and Nanjing), West (Chongqing, Deyang, and Xi'an), South (Shenzhen, Haikou, and Changsha), and center (Wuhan and Zhengzhou). All the children with ASD from the hospital rehabilitation department or developmental behavioral pediatrics and rehabilitation training institutions were enrolled in this study. Diagnoses were made by psychologists or developmental pediatricians at children's hospitals after various structured interviews based on the criteria for ASD defined in the <emph>Diagnostic and Statistical Manual of Mental Disorders, 5th Edition</emph> (DSM-5) (APA 2013). Each diagnosis was verified using a Children Autism Rating Scale (CARS). Serving as our control were 1,206 typically developing (TD) children recruited from online volunteers and local preschools who met the following inclusion criteria: (<reflink idref="bib1" id="ref12">1</reflink>) absence of ASD and motor or language impairments, or diagnosis of social developmental disorders, and (<reflink idref="bib2" id="ref13">2</reflink>) no family history of ASD in first- or second-degree relatives, according to the reports of their parents and teachers. Any individuals with diagnosed other developmental or neurological disorders such as Fragile X, Rett's syndrome, seizures and cerebral palsy; significant sensory or motor impairment; major physical/medical symptoms; serious head injury; acute or chronic infection in the previous three months; or being unwilling to participate were excluded from the study.</p> <p>Out of the 2762 children were recruited in this study, 2428 children were finally included after excluding those who did not fill in the questionnaire and did not complete the six-item Gastrointestinal Severity Index (6-GSI) assessment. Figure 1 presents a flow chart of the sample screening process.</p> <p>Graph: Fig. 1 The flow chart of the sample screening process. (ASD, autism spectrum disorder; TD, typically developing)</p> <p>The research program was approved by the ethics committee of the Children's Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121 and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2000031194). Participation in this study was voluntary, and parents provided informed consent forms for all the participants.</p> <hd id="AN0180153909-5">Anthropometric Measures</hd> <p>Three standardized trained anthropometrists conducted anthropometric examinations using a digital scale and a wall height-measuring device (Changzhou Wujin Weighing Instrument Co., Ltd). The participants wore minimal clothing and no shoes. The weight measurement values were accurate to within 0.05 kg, and height measurement values were accurate to within 0.1 cm. The Z scores for weight-for-height (Z<subs>WA</subs>), height-for-age (Z<subs>HA</subs>), and body mass index (BMI; Z<subs>BMIA</subs>) were calculated using WHO Anthro and AnthroPlus software (World Health Organization, 2009; Anthro for Personal Computers, Version 3.01: Software for Assessing Growth and Development of the World's Children).</p> <hd id="AN0180153909-6">Questionnaires</hd> <p>Trained investigators collected demographic information through face-to-face interviews with caregivers of children with ASD and TD children. Questions regarding intestinal symptoms such as constipation, stool smell [unusual (foul, irritating, etc.) odor], diarrhea, stool consistency, flatulence and abdominal pain were based on 6-GSI (Schneider et al., [<reflink idref="bib22" id="ref14">22</reflink>]). Each symptom was assigned a score of 0, 1, or 2 based on its frequency per week. A score of 0 was interpreted as the absence of the symptom while 1 and 2 denoted presences of the symptom with differing severity. A score greater than or equal to 1 indicated that the existence of intestinal symptoms, with 1 as mild intestinal symptom and 2 as severe intestinal symptoms. Caregivers assessed intestinal symptoms according to the child's condition in the prior 2–3 months. The CARS, Social Responsiveness Scale (SRS), and Aberrant Behavior Checklist (ABC) were used to assess the clinical symptoms of children with ASD. The CARS comprised 15 items, each scored on a 4-point scale, with normality defined as a score less than 30 (Rellini, Tortolani, Trillo, Carbone, & Montecchi, [<reflink idref="bib21" id="ref15">21</reflink>]). The SRS scale is composed of 65 items and contains five subscales, specifically: social awareness, social motivation, social communication, social cognition, and autistic mannerisms. Each item is scored on a scale of 1–4 according to the child's performance (in the past 6 months), with normality defined as a score less than 65 (Cen et al., [<reflink idref="bib3" id="ref16">3</reflink>]). The ABC scale contains 57 items categorized into five groups: sensory, relating, body and object use, language, and social and self-help. The total possible score is 158, with normality defined as a score less than 67, though this study used a screening cut-off of 53 (Rellini et al., [<reflink idref="bib21" id="ref17">21</reflink>]). The SRS and ABC scales were conducted by caregivers of children with ASD as instructed by the trained investigators. The developmental pediatrician or child psychologist assessed the CARS.</p> <hd id="AN0180153909-7">Statistical Analyses</hd> <p>SPSS Statistics 22.0 software (IBM Corporation, Armonk, NY, USA) was used for statistical analyses of data. Before data analysis, each dataset was first tested for distribution using the Kolmogorov-Smirnov goodness-of-fit test. Continuous variables were represented as mean ± standard deviation or median ± interquartile range (IQR). Categorical variables were described by frequencies or percentages. Group differences were compared by independent-samples <emph>t</emph>-test or Wilcoxon rank-sum test for continuous variables and chi-squared test or Fisher's exact test for categorical variables. The covariance analysis model was used to analyze the effect of intestinal symptoms on the total and subscale scores of ABC, SRS, and CARS, with age as a covariant. A two-sided <emph>P</emph> value less than 0.05 indicated a statistically significant difference.</p> <hd id="AN0180153909-8">Results</hd> <p></p> <hd id="AN0180153909-9">Sociodemographic and Physical Development Characteristics</hd> <p>In total, 1,222 children with ASD (992 boys and 230 girls) and 1,206 TD children (797 boys and 409 girls) participated in this study. The median age of the children with ASD and TD children was 4.01 (3.19–5.04) years, and 4.49 (3.45–5.47) years, respectively. Significant differences in age and sex were observed between the two groups (<emph>P</emph> < 0.001). No statistically significant differences were observed in the Z-scores of height, weight, and BMI between the two groups in either boys or girls (Table 1). These results suggested that the physical status of the children with ASD was not different from that of TD children.</p> <p>Table 1 Demographic characteristics of the participants in TD and ASD groups</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Variable</p></th><th align="left"><p>TD(N = 1206)</p></th><th align="left"><p>ASD(N = 1222)</p></th><th align="left"><p><inline-graphic href="10803_2023_6122_Article_IEq1.gif" /></p></th><th align="left"><p><italic>P</italic>-value</p></th></tr></thead><tbody><tr><td align="left"><p>Gender,n(%)</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Boys</p></td><td align="left"><p>797(66.09%)</p></td><td align="left"><p>992(81.18%)</p></td><td align="left" rowspan="2"><p>71.295</p></td><td align="left" rowspan="2"><p><0.001</p></td></tr><tr><td align="left"><p>Girls</p></td><td align="left"><p>409(33.91%)</p></td><td align="left"><p>230(18.82%)</p></td></tr><tr><td align="left"><p>Age (years), Median (IQR)</p></td><td align="left"><p>4.49(3.45–5.47)</p></td><td align="left"><p>4.01(3.19–5.04)</p></td><td align="left"><p>-5.813</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Boys</p></td><td align="left"><p>N = 786</p></td><td align="left"><p> N = 819</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Z<sub>HA</sub>, Median (IQR)</p></td><td align="left"><p>0.10(-0.64-0.82)</p></td><td align="left"><p>0.24(-0.52-0.91)</p></td><td align="left"><p>-1.935</p></td><td align="left"><p>0.053</p></td></tr><tr><td align="left"><p> Z<sub>WA</sub>, Median (IQR)</p></td><td align="left"><p>0.26(-0.39-0.88)</p></td><td align="left"><p>0.38(-0.34-1.08)</p></td><td align="left"><p>-1.690</p></td><td align="left"><p>0.091</p></td></tr><tr><td align="left"><p>Z<sub>BMIA</sub>, Median (IQR)</p></td><td align="left"><p>0.30(-0.42-1.10)</p></td><td align="left"><p>0.30(-0.42-1.13)</p></td><td align="left"><p>-0.285</p></td><td align="left"><p>0.776</p></td></tr><tr><td align="left"><p>Girls</p></td><td align="left"><p>N = 395</p></td><td align="left"><p> N = 182</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Z<sub>HA</sub>, Median (IQR)</p></td><td align="left"><p>0.07(-0.66-0.65)</p></td><td align="left"><p>0.21(-0.51-0.93)</p></td><td align="left"><p>-1.811</p></td><td align="left"><p>0.070</p></td></tr><tr><td align="left"><p>Z<sub>WA</sub>, Median (IQR)</p></td><td align="left"><p>0.17(-0.51-0.71)</p></td><td align="left"><p>0.12(-0.49-0.78)</p></td><td align="left"><p>-0.296</p></td><td align="left"><p>0.767</p></td></tr><tr><td align="left"><p>Z<sub>BMIA</sub>, Median (IQR)</p></td><td align="left"><p>0.12(-0.53-0.82)</p></td><td align="left"><p>0.10(-0.73-0.73)</p></td><td align="left"><p>1.331</p></td><td align="left"><p>0.183</p></td></tr></tbody></table> </ephtml> </p> <p>ASD, autism spectrum disorder; TD, typically developing; IQR, interquartile range. Z<subs>HA</subs>, Z-scores for height; Z<subs>WA</subs>, Z-scores for weight; Z<subs>BMIA</subs>, Z-scores for BMI Data was shown as Median (IQR), mean or number (percentage). Chi-square test and Mann-Whitney U test were used in the analysis.</p> <hd id="AN0180153909-10">Children with ASD had a Higher Prevalence of Intestinal Symptoms, Especially Constipation and...</hd> <p>As depicted in Table2, 53.60% of children in the ASD group reported having at least one intestinal symptom compared with 41.29% of TD children (<emph>P</emph> < 0.001). Children with ASD had significantly greater rates of constipation and stool smell compared to TD children (40.10% vs. 25.62%, 17.02% vs. 9.29%, <emph>P</emph> < 0.001 for both), which were the most frequent intestinal symptoms in children with ASD (n = 490 and 208, respectively). The prevalence of abdominal pain was significantly lower in children with ASD than in TD children (7.45% vs. 11.77%, <emph>P</emph> < 0.001). This study might have underestimated the prevalence of abdominal pain in children with ASD, because many children with ASD have language impairment and might not have correctly described abdominal pain.</p> <p>Table 2 Comparison of intestinal symptoms between the TD and the ASD groups.</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Symptoms</p></th><th align="left"><p>TD (N = 1206) n (%)</p></th><th align="left"><p>ASD (N = 1222) n (%)</p></th><th align="left"><p>χ<sup>2</sup></p></th><th align="left"><p><italic>P-</italic>value</p></th></tr></thead><tbody><tr><td align="left"><p>Flatulence</p></td><td align="left"><p>82(6.80)</p></td><td align="left"><p>105(8.59)</p></td><td align="left"><p>2.745</p></td><td align="left"><p>0.098</p></td></tr><tr><td align="left"><p>Constipation</p></td><td align="left"><p>309(25.62)</p></td><td align="left"><p>490(40.10)</p></td><td align="left"><p>57.612</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Diarrhea</p></td><td align="left"><p>115(9.54)</p></td><td align="left"><p>128(10.48)</p></td><td align="left"><p>0.594</p></td><td align="left"><p>0.441</p></td></tr><tr><td align="left"><p>Stool consistency</p></td><td align="left"><p>109(9.04)</p></td><td align="left"><p>114(9.33)</p></td><td align="left"><p>0.062</p></td><td align="left"><p>0.804</p></td></tr><tr><td align="left"><p>Stool smell</p></td><td align="left"><p>112(9.29)</p></td><td align="left"><p>208(17.02)</p></td><td align="left"><p>31.732</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Abdominal pain</p></td><td align="left"><p>142(11.77)</p></td><td align="left"><p>91(7.45)</p></td><td align="left"><p>13.103</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Total intestinal symptoms</p></td><td align="left"><p>498(41.29)</p></td><td align="left"><p>655(53.60)</p></td><td align="left"><p>36.867</p></td><td align="left"><p><0.001</p></td></tr></tbody></table> </ephtml> </p> <p>ASD, autism spectrum disorder; TD, typically developing; Data was shown as number (percentage). Chi-square test was used in the analysis.</p> <hd id="AN0180153909-11">Comparison of Intestinal Symptoms in Children with ASD and TD Children of Different Sexes</hd> <p>We further analyzed differences in the prevalence of intestinal symptoms in children with ASD and TD children across sexes. The prevalence of constipation, Stool smell, and total intestinal symptoms were significantly higher in children with ASD than in TD children for both boys and girls (<emph>P</emph> < 0.001 for all). Among boys, the rate of abdominal pain was significantly lower in children with ASD than that in TD children (<emph>P</emph> = 0.001), while no difference was found in girls (Table 3).</p> <p>Table 3 Comparison of intestinal symptoms in the ASD and TD groups of different sexes</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2"><p>Symptoms</p></th><th align="left" colspan="4"><p>Boys(N = 1789)</p></th><th align="left" colspan="4"><p>Girls(N = 639)</p></th></tr><tr><th align="left"><p>TD(N = 797) n (%)</p></th><th align="left"><p>ASD(N = 992) n (%)</p></th><th align="left"><p>χ<sup>2</sup></p></th><th align="left"><p><italic>P-</italic>value</p></th><th align="left"><p>TD(N = 409) n (%)</p></th><th align="left"><p>ASD(N = 230) n (%)</p></th><th align="left"><p>χ<sup>2</sup></p></th><th align="left"><p><italic>P-</italic>value</p></th></tr></thead><tbody><tr><td align="left"><p>Flatulence</p></td><td align="left"><p>58(7.28)</p></td><td align="left"><p>86(8.67)</p></td><td align="left"><p>1.157</p></td><td align="left"><p>0.282</p></td><td align="left"><p>24(5.87)</p></td><td align="left"><p>19(8.26)</p></td><td align="left"><p>2.745</p></td><td align="left"><p>0.098</p></td></tr><tr><td align="left"><p>Constipation</p></td><td align="left"><p>192(24.09)</p></td><td align="left"><p>391(39.42)</p></td><td align="left"><p>47.246</p></td><td align="left"><p><0.001</p></td><td align="left"><p>117(28.61)</p></td><td align="left"><p>99(43.04)</p></td><td align="left"><p>13.713</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Diarrhea</p></td><td align="left"><p>85(10.67)</p></td><td align="left"><p>109(10.99)</p></td><td align="left"><p>0.048</p></td><td align="left"><p>0.827</p></td><td align="left"><p>30(7.34)</p></td><td align="left"><p>19(8.26)</p></td><td align="left"><p>0.178</p></td><td align="left"><p>0.673</p></td></tr><tr><td align="left"><p>Stool consistency</p></td><td align="left"><p>82(10.29)</p></td><td align="left"><p>97(9.78)</p></td><td align="left"><p>0.128</p></td><td align="left"><p>0.721</p></td><td align="left"><p>27(6.60)</p></td><td align="left"><p>17(7.39)</p></td><td align="left"><p>0.143</p></td><td align="left"><p>0.705</p></td></tr><tr><td align="left"><p>Stool smell</p></td><td align="left"><p>79(9.91)</p></td><td align="left"><p>168(16.94)</p></td><td align="left"><p>18.318</p></td><td align="left"><p><0.001</p></td><td align="left"><p>33(8.07)</p></td><td align="left"><p>40(17.39)</p></td><td align="left"><p>12.645</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Abdominal pain</p></td><td align="left"><p>100(12.55)</p></td><td align="left"><p>76(7.66)</p></td><td align="left"><p>11.893</p></td><td align="left"><p>0.001</p></td><td align="left"><p>42(10.27)</p></td><td align="left"><p>15(6.52)</p></td><td align="left"><p>2.544</p></td><td align="left"><p>0.111</p></td></tr><tr><td align="left"><p>Total intestinal symptoms</p></td><td align="left"><p>332(41.66)</p></td><td align="left"><p>525(52.92)</p></td><td align="left"><p>22.481</p></td><td align="left"><p><0.001</p></td><td align="left"><p>166(40.59)</p></td><td align="left"><p>130(56.52)</p></td><td align="left"><p>15.034</p></td><td align="left"><p><0.001</p></td></tr></tbody></table> </ephtml> </p> <p>ASD, autism spectrum disorder; TD, typically developing; Data was shown as number (percentage). Chi-square test was used in the analysis.</p> <hd id="AN0180153909-12">Comparison of Intestinal Symptoms in Children with ASD of Different Sexes</hd> <p>Studies have shown that the sex ratio for children with ASD is about 4:1, indicating a severe sex bias. Therefore, we conducted a subgroup comparison by sex among children with ASD. We found that there was no significant difference in the detection rates of various intestinal problems between boys and girls (Table 4).</p> <p>Table 4 Comparison of intestinal symptoms in ASD children of different gender</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Symptoms</p></th><th align="left"><p>Boys (N = 992)</p><p>n (%)</p></th><th align="left"><p>Girls (N = 230)</p><p> n (%)</p></th><th align="left"><p>χ<sup>2</sup></p></th><th align="left"><p><italic>P-</italic>value</p></th></tr></thead><tbody><tr><td align="left"><p>Flatulence</p></td><td align="left"><p>86(8.67)</p></td><td align="left"><p>19(8.26)</p></td><td align="left"><p>0.040</p></td><td align="left"><p>0.842</p></td></tr><tr><td align="left"><p>Constipation</p></td><td align="left"><p>391(39.42)</p></td><td align="left"><p>99(43.04)</p></td><td align="left"><p>1.023</p></td><td align="left"><p>0.312</p></td></tr><tr><td align="left"><p>Diarrhea</p></td><td align="left"><p>109(10.99)</p></td><td align="left"><p>19(8.26)</p></td><td align="left"><p>1.481</p></td><td align="left"><p>0.224</p></td></tr><tr><td align="left"><p>Stool consistency</p></td><td align="left"><p>97(9.78)</p></td><td align="left"><p>17(7.39)</p></td><td align="left"><p>1.258</p></td><td align="left"><p>0.262</p></td></tr><tr><td align="left"><p>Stool smell</p></td><td align="left"><p>168(16.94)</p></td><td align="left"><p>40(17.39)</p></td><td align="left"><p>0.027</p></td><td align="left"><p>0.868</p></td></tr><tr><td align="left"><p>Abdominal pain</p></td><td align="left"><p>76(7.66)</p></td><td align="left"><p>15(6.52)</p></td><td align="left"><p>0.352</p></td><td align="left"><p>0.676</p></td></tr><tr><td align="left"><p>Total intestinal symptoms</p></td><td align="left"><p>525(52.92)</p></td><td align="left"><p>130(56.52)</p></td><td align="left"><p>0.972</p></td><td align="left"><p>0.324</p></td></tr></tbody></table> </ephtml> </p> <p>ASD, autism spectrum disorder; TD, typically developing; Data was shown as number (percentage). Chi-square test was used in the analysis.</p> <hd id="AN0180153909-13">Association of the Intestinal Symptoms with ABC, SRS, and CARS Scores in Children with ASD</hd> <p>As shown in Table 5, children with ASD were divided into two groups: without intestinal symptoms and with intestinal symptoms according to intestinal symptoms. We used covariance analysis to analyze the effect of these symptoms on the scores of ABC, SRS, and CARS with age as a covariant. The ABC total score (<emph>P</emph> < 0.001), as well as the scores of each of its five categories: sensory (<emph>P</emph> = 0.002), relating (<emph>P</emph> = 0.022), body and object use (<emph>P</emph> = 0.001), language (<emph>P</emph> = 0.005), and social and self-help (<emph>P</emph> = 0.001) were significantly higher in children with ASD with intestinal symptoms. Moreover, their SRS total score (<emph>P</emph> < 0.001) and the subscale scores of social awareness (<emph>P</emph> = 0.006), social cognition (<emph>P</emph> = 0.002), social communication (<emph>P</emph> = 0.001), and autistic mannerisms (<emph>P</emph> < 0.001) were significantly increased in ASD children with intestinal symptoms. These results suggested that children with ASD with intestinal problems had higher symptom scores and more severe symptoms.</p> <p>Table 5 Comparison of the scales scores between the ASD children with and without intestinal symptoms</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Scale scores</p></th><th align="left"><p>Non-intestinal symptoms</p></th><th align="left"><p>Intestinal symptoms</p></th><th align="left"><p><italic>F</italic></p></th><th align="left"><p><italic>P-value</italic></p></th></tr></thead><tbody><tr><td align="left"><p>ABC scale scores</p></td><td align="left"><p>(N = 523)</p></td><td align="left"><p>(N = 578)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Sensory</p></td><td align="left"><p>7.32 ± 5.15</p></td><td align="left"><p>8.32 ± 5.39</p></td><td align="left"><p>10.117</p></td><td align="left"><p>0.002</p></td></tr><tr><td align="left"><p>Relating</p></td><td align="left"><p>12.68 ± 8.12</p></td><td align="left"><p>13.75 ± 7.33</p></td><td align="left"><p>5.271</p></td><td align="left"><p>0.022</p></td></tr><tr><td align="left"><p>Body and object use</p></td><td align="left"><p>7.66 ± 6.78</p></td><td align="left"><p>9.12 ± 7.66</p></td><td align="left"><p>11.291</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Language</p></td><td align="left"><p>10.91 ± 6.89</p></td><td align="left"><p>12.07 ± 7.41</p></td><td align="left"><p>7.976</p></td><td align="left"><p>0.005</p></td></tr><tr><td align="left"><p>Social self-help</p></td><td align="left"><p>10.34 ± 4.99</p></td><td align="left"><p>11.39 ± 5.19</p></td><td align="left"><p>11.737</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>48.88 ± 23.07</p></td><td align="left"><p>54.66 ± 23.40</p></td><td align="left"><p>17.215</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>SRS scale scores</p></td><td align="left"><p>(N = 933)</p></td><td align="left"><p>(N = 168)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Social awareness</p></td><td align="left"><p>11.29 ± 3.21</p></td><td align="left"><p>11.82 ± 3.29</p></td><td align="left"><p>7.652</p></td><td align="left"><p>0.006</p></td></tr><tr><td align="left"><p>Social cognition</p></td><td align="left"><p>17.77 ± 4.47</p></td><td align="left"><p>18.59 ± 4.57</p></td><td align="left"><p>9.884</p></td><td align="left"><p>0.002</p></td></tr><tr><td align="left"><p>Social communication</p></td><td align="left"><p>31.86 ± 8.61</p></td><td align="left"><p>33.53 ± 8.81</p></td><td align="left"><p>10.774</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Social motivation</p></td><td align="left"><p>15.09 ± 5.09</p></td><td align="left"><p>15.53 ± 4.94</p></td><td align="left"><p>2.226</p></td><td align="left"><p>0.136</p></td></tr><tr><td align="left"><p>Autistic mannerisms</p></td><td align="left"><p>12.91 ± 5.86</p></td><td align="left"><p>14.25 ± 6.00</p></td><td align="left"><p>15.940</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>88.96 ± 22.27</p></td><td align="left"><p>93.73 ± 22.66</p></td><td align="left"><p>13.408</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>CARS scale scores</p></td><td align="left"><p>(N = 496)</p></td><td align="left"><p>(N = 560)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>33.09 ± 6.66</p></td><td align="left"><p>33.45 ± 7.01</p></td><td align="left"><p>0.792</p></td><td align="left"><p>0.374</p></td></tr></tbody></table> </ephtml> </p> <p>TD, typically developing; ASD, autism spectrum disorder; ABC, Autism Behavior Checklist; SRS, Social Responsiveness Scale; CARS, Child Autism Rating Scale. Data was shown as mean ± standard deviation. The covariance analysis model was used to analyze the effect of intestinal symptoms on the ABC, SRS, and CARS total and subscale scores with age as a covariant.</p> <hd id="AN0180153909-14">Association of Constipation with ABC, SRS, and CARS Scores in Children with ASD</hd> <p>We compared the core symptom scores of children with ASD with and without constipation symptoms. Compared with ASD children without constipation, the ABC total score (<emph>P</emph> = 0.001) and category scores of sensory (<emph>P</emph> = 0.006), body and object use (<emph>P</emph> = 0.003), and language (<emph>P</emph> = 0.011) of ASD children with constipation were significantly higher (Table 6). The SRS total score (<emph>P</emph> = 0.023) and the subscale scores of autistic mannerisms (<emph>P</emph> = 0.001) were significantly increased in ASD children with constipation symptoms. These results indicated that ASD children with constipation had higher symptom scores and more severe core symptoms.</p> <p>Table 6 Comparison of the scales scores between the ASD children with and without constipation symptoms</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Scale scores</p></th><th align="left"><p>Non-constipation</p></th><th align="left"><p>Constipation</p></th><th align="left"><p><italic>F</italic></p></th><th align="left"><p><italic>P-value</italic></p></th></tr></thead><tbody><tr><td align="left"><p>ABC scale scores</p></td><td align="left"><p>(N = 653)</p></td><td align="left"><p>(N = 448)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Sensory</p></td><td align="left"><p>7.48 ± 5.14</p></td><td align="left"><p>8.38 ± 5.49</p></td><td align="left"><p>7.586</p></td><td align="left"><p>0.006</p></td></tr><tr><td align="left"><p>Relating</p></td><td align="left"><p>12.97 ± 7.75</p></td><td align="left"><p>13.63 ± 7.69</p></td><td align="left"><p>1.917</p></td><td align="left"><p>0.166</p></td></tr><tr><td align="left"><p>Body and object use</p></td><td align="left"><p>7.88 ± 6.88</p></td><td align="left"><p>9.13 ± 7.77</p></td><td align="left"><p>8.987</p></td><td align="left"><p>0.003</p></td></tr><tr><td align="left"><p>Language</p></td><td align="left"><p>11.07 ± 6.93</p></td><td align="left"><p>12.18 ± 7.50</p></td><td align="left"><p>6.495</p></td><td align="left"><p>0.011</p></td></tr><tr><td align="left"><p>Social self-help</p></td><td align="left"><p>10.66 ± 5.06</p></td><td align="left"><p>11.23 ± 5.21</p></td><td align="left"><p>3.279</p></td><td align="left"><p>0.070</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>50.05 ± 22.59</p></td><td align="left"><p>54.63 ± 24.30</p></td><td align="left"><p>10.235</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>SRS scale scores</p></td><td align="left"><p>(N = 664)</p></td><td align="left"><p>(N = 452)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Social awareness</p></td><td align="left"><p>11.44 ± 3.08</p></td><td align="left"><p>11.77 ± 3.50</p></td><td align="left"><p>2.797</p></td><td align="left"><p>0.095</p></td></tr><tr><td align="left"><p>Social cognition</p></td><td align="left"><p>18.04 ± 4.51</p></td><td align="left"><p>18.46 ± 4.58</p></td><td align="left"><p>2.231</p></td><td align="left"><p>0.136</p></td></tr><tr><td align="left"><p>Social communication</p></td><td align="left"><p>32.34 ± 8.50</p></td><td align="left"><p>33.37 ± 9.09</p></td><td align="left"><p>3.760</p></td><td align="left"><p>0.053</p></td></tr><tr><td align="left"><p>Social motivation</p></td><td align="left"><p>15.24 ± 5.11</p></td><td align="left"><p>15.46 ± 4.87</p></td><td align="left"><p>0.509</p></td><td align="left"><p>0.476</p></td></tr><tr><td align="left"><p>Autistic mannerisms</p></td><td align="left"><p>13.16 ± 5.83</p></td><td align="left"><p>14.32 ± 6.11</p></td><td align="left"><p>10.539</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>90.26 ± 22.03</p></td><td align="left"><p>93.38 ± 22.30</p></td><td align="left"><p>5.207</p></td><td align="left"><p>0.023</p></td></tr><tr><td align="left"><p>CARS scale scores</p></td><td align="left"><p>(N = 641)</p></td><td align="left"><p>(N = 415)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>33.15 ± 6.73</p></td><td align="left"><p>33.49 ± 7.03</p></td><td align="left"><p>0.594</p></td><td align="left"><p>0.441</p></td></tr></tbody></table> </ephtml> </p> <p>TD, typically developing; ASD, autism spectrum disorder; ABC, Autism Behavior Checklist; SRS, Social Responsiveness Scale; CARS, Child Autism Rating Scale. Data was shown as mean ± standard deviation. The covariance analysis model was used to analyze the effect of constipation on the ABC, SRS, and CARS total and subscale scores with age as a covariant.</p> <hd id="AN0180153909-15">Association of the Stool Smell with ABC, SRS, and CARS Scores in Children with ASD</hd> <p>As shown in Table 7, the ABC total score and the subscale scores of sensory, relating, body and object use, language, and social and self-help of ASD children with stool smell were significantly increased (<emph>P</emph> ≤ 0.001 for all). The SRS total score (<emph>P</emph> < 0.001) and subscale scores of social awareness (<emph>P</emph> = 0.006), social cognition (<emph>P</emph> < 0.001), social communication (<emph>P</emph> = 0.001), social motivation (<emph>P</emph> = 0.015), and autistic mannerisms (<emph>P</emph> < 0.001) were significantly increased. The total score of the CARS scale was significantly higher (<emph>P</emph> = 0.046). Overall, these results indicated that the comorbidity of stool smell might aggravate autistic symptoms in children with ASD.</p> <p>Table 7 Comparison of the scales scores between the ASD children with and without Stool smell</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left"><p>Scale scores</p></th><th align="left"><p>Non-stool smell</p></th><th align="left"><p>Stool smell</p></th><th align="left"><p><italic>F</italic></p></th><th align="left"><p><italic>P-value</italic></p></th></tr></thead><tbody><tr><td align="left"><p>ABC scale scores</p></td><td align="left"><p>(N = 933)</p></td><td align="left"><p>(N = 168)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Sensory</p></td><td align="left"><p>7.60 ± 5.26</p></td><td align="left"><p>9.22 ± 5.31</p></td><td align="left"><p>13.387</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Relating</p></td><td align="left"><p>12.84 ± 7.72</p></td><td align="left"><p>15.49 ± 7.40</p></td><td align="left"><p>17.142</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Body and object use</p></td><td align="left"><p>8.04 ± 7.00</p></td><td align="left"><p>10.60 ± 8.05</p></td><td align="left"><p>17.750</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Language</p></td><td align="left"><p>11.21 ± 7.09</p></td><td align="left"><p>13.24 ± 7.53</p></td><td align="left"><p>11.290</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Social self-help</p></td><td align="left"><p>10.56 ± 5.04</p></td><td align="left"><p>12.73 ± 5.21</p></td><td align="left"><p>26.364</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>50.23 ± 23.08</p></td><td align="left"><p>61.27 ± 23.07</p></td><td align="left"><p>32.418</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>SRS scale scores</p></td><td align="left"><p>(N = 927)</p></td><td align="left"><p>(N = 189)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Social awareness</p></td><td align="left"><p>11.45 ± 3.29</p></td><td align="left"><p>12.17 ± 3.04</p></td><td align="left"><p>7.703</p></td><td align="left"><p>0.006</p></td></tr><tr><td align="left"><p>Social cognition</p></td><td align="left"><p>18.00 ± 4.56</p></td><td align="left"><p>19.27 ± 4.29</p></td><td align="left"><p>12.845</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Social communication</p></td><td align="left"><p>32.35 ± 8.70</p></td><td align="left"><p>34.74 ± 8.78</p></td><td align="left"><p>11.992</p></td><td align="left"><p>0.001</p></td></tr><tr><td align="left"><p>Social motivation</p></td><td align="left"><p>15.16 ± 4.95</p></td><td align="left"><p>16.13 ± 5.26</p></td><td align="left"><p>5.929</p></td><td align="left"><p>0.015</p></td></tr><tr><td align="left"><p>Autistic mannerisms</p></td><td align="left"><p>13.32 ± 5.87</p></td><td align="left"><p>15.14 ± 6.21</p></td><td align="left"><p>15.854</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>90.31 ± 22.42</p></td><td align="left"><p>97.44 ± 22.56</p></td><td align="left"><p>16.404</p></td><td align="left"><p><0.001</p></td></tr><tr><td align="left"><p>CARS scale scores</p></td><td align="left"><p>(N = 882)</p></td><td align="left"><p>(N = 174)</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Total score</p></td><td align="left"><p>33.10 ± 6.85</p></td><td align="left"><p>34.22 ± 6.77</p></td><td align="left"><p>4.003</p></td><td align="left"><p>0.046</p></td></tr></tbody></table> </ephtml> </p> <p>TD, typically developing; ASD, autism spectrum disorder; ABC, Autism Behavior Checklist; SRS, Social Responsiveness Scale; CARS, Child Autism Rating Scale. Data was shown as mean ± standard deviation. The covariance analysis model was used to analyze the effect of stool smell on the ABC, SRS, and CARS total and subscale scores with age as a covariant.</p> <hd id="AN0180153909-16">Discussion</hd> <p>In recent years, several epidemiological studies have shown increasing prevalence of ASD (Maenner Mj Fau - Shaw et al., [<reflink idref="bib23" id="ref18">23</reflink>]; Maenner et al., [<reflink idref="bib17" id="ref19">17</reflink>]; Zhou et al., [<reflink idref="bib27" id="ref20">27</reflink>]). Studies also showed that ASD often presented with multiple comorbidities (Al-Beltagi, [<reflink idref="bib1" id="ref21">1</reflink>]; Lord et al., [<reflink idref="bib14" id="ref22">14</reflink>]). An increasing number of scholars emphasize the identification and intervention of ASD comorbidities. Intestinal symptoms are the most common comorbidities of ASD. These symptoms affect the core symptoms of ASD and intervention effects and have, therefore become a research hotspot (Srikantha & Mohajeri, [<reflink idref="bib24" id="ref23">24</reflink>]). Some scholars believe that ASD with intestinal comorbidities may be a subtype of ASD (Brown et al., [<reflink idref="bib2" id="ref24">2</reflink>]). In this study, we conducted a nationwide multicenter cross-sectional survey in China focused on the rate of intestinal symptoms in children with ASD aged 2–7 years and its associations with the core symptom scores of these ASD.</p> <p>Some studies have reported that children with ASD experience insufficient nutritional intake and poor physical growth due to their special dietary patterns (Liu et al., [<reflink idref="bib13" id="ref25">13</reflink>]). Other scholars have also found that children with ASD especially prefer a high-fat diet due to their picky eating behavior, leading to significantly higher weight and obesity in children with ASD than in TD children (Dhaliwal, Orsso, Richard, Haqq, & Zwaigenbaum, [<reflink idref="bib6" id="ref26">6</reflink>]). The present study found no significant difference in the Z score of children's physical development (Z<subs>HA</subs>, Z<subs>WA</subs>, and Z<subs>BMIA</subs>) between the children with ASD and TD children, which was a key indicator of children's nutritional status. No differences in weight, height and BMI between children with ASD and controls reflected the energy intake in the two groups. Despite this, children with ASD were at an increased risk of deficiency of micronutrients and dietary fiber due to their selective dietary patterns.</p> <p>In the current study, the prevalence of total intestinal symptoms in 1222 children with ASD was found to be 53.60%. Among intestinal symptoms, constipation was the most common (40.10% of the study cohort), followed by Stool smell, diarrhea, and various fecal traits. These rates were all significantly higher than those of TD children (see Tables 2 and 3). These results were consistent with those of a previous study involving 328 children with ASD in Chongqing (Jiang et al., [<reflink idref="bib10" id="ref27">10</reflink>]). Studies reported that the most common gastrointestinal symptoms in children with ASD were constipation, diarrhea, and abdominal pain (Madra, Ringel, & Margolis, [<reflink idref="bib16" id="ref28">16</reflink>]; McElhanon et al., [<reflink idref="bib20" id="ref29">20</reflink>]). Except for constipation, the proportion of other intestinal comorbidities were somewhat different in our study. Holingue et al., in a systematic review of the literature on gastrointestinal comorbidities in children with ASD published from 1980 to 2017, found that the prevalence of ASD with constipation ranged from 4.3 to 45.5%, with diarrhea from 2.3 to 75.6%, and with multiple various gastrointestinal symptoms from 4.2 to 96.8% (Holingue, Newill, Lee, Pasricha, & Daniele Fallin, [<reflink idref="bib8" id="ref30">8</reflink>]). Due to differences in subjects, definitions, and measurement methods, reported gastrointestinal symptoms varied widely among these studies. The results of this study suggested that, despite intestinal dysfunction being more common in children with ASD, the detection rate of abdominal pain was significantly lower in children with ASD than in TD children (see Tables 2 and 3), which was inconsistent with the findings of previous studies (Lanyi et al., [<reflink idref="bib12" id="ref31">12</reflink>]). This might be because our study found that the prevalence of language delay in children with ASD was 73.93%, and ASD children might not express their abdominal pain well, resulting in underestimation of the issue by parents or relevant professionals. When children with ASD exhibit unexplained strange postures, sleep disorders, food intolerances, and aggressive or self-harming behaviors, evaluators should focus on assessing and, if necessary, intervening in gastrointestinal symptoms in children with ASD. Therefore, in the future, a questionnaire for intestinal symptoms in children with ASD should be developed (which may include behavioral indicators of discomfort, such as aggression, self-injury, and abdominal thrusting, etc.), so that follow-up research can use standardized, reliable, and effective intestinal symptom assessment tools to investigate and obtain reliable findings.</p> <p>Children with ASD with intestinal symptoms are more likely to exhibit with anxiety symptoms, somatic symptoms (such as unexplained body aches and headaches), and behavioral issues (Madra et al., [<reflink idref="bib16" id="ref32">16</reflink>]). Our previous single-center study findings also indicated that these children display more severe repetitive stereotyped behaviors, as well as emotional and behavioral problems (Jiang et al., [<reflink idref="bib10" id="ref33">10</reflink>]). Chaidez et al. demonstrated that children with ASD who frequently reported gastrointestinal symptoms scored worse on irritability, social withdrawal, stereotyping, and hyperactivity (Chaidez, Hansen, & Hertz-Picciotto, [<reflink idref="bib4" id="ref34">4</reflink>]). Similarly, Marler et al. also found that children with ASD with constipation had more prominent repetitive and stereotypical behaviors, as identified through the parental report questionnaire (Marler et al., [<reflink idref="bib19" id="ref35">19</reflink>]). We further analyzed the correlation between the most common intestinal symptoms (constipation, stool smell, and total intestinal problems) and CARS, ABC, and SRS scores in children with ASD to clarify the impact of these highly prevalent intestinal problems on the behavior of children with ASD. Our data indicated that the total score of each scale and scores of multiple subscales were significantly higher in ASD children with intestinal symptoms, which confirmed these children also had severe core symptoms. Further studies are needed to understand the mechanism underlying this phenomenon. Our previous studies have found that changes in the microbiome and its metabolites might affect the social behavior of ASD through the gut-brain axis in ASD animal models and children diagnosed with ASD(Wang et al., [<reflink idref="bib25" id="ref36">25</reflink>]; Xiao et al., [<reflink idref="bib26" id="ref37">26</reflink>]; Zhu et al., [<reflink idref="bib28" id="ref38">28</reflink>]). Therefore, we speculated that it might be due to abnormal microbiota and its metabolites in children with ASD, accompanied by gastrointestinal dysfunction, which then affected their clinical symptoms through the microbiota gut-brain axis.</p> <p>The results of our study are limited by the lack of standardized and validated methods for assessing intestinal symptoms of ASD. As previously discussed, the prevalence of intestinal symptoms in children with ASD may be underestimated due to the frequency of communication problems and language development delays therein. Although the present study drew data from hospitals in 13 different cities across China, only one hospital with good diagnostic ability was selected for investigation in each city. This may not be representative enough and may have some selection bias. Finally, this being a cross-sectional study, we did not follow up on the long-term impact of various intestinal symptoms on clinical core symptoms and rehabilitation in children with ASD.</p> <hd id="AN0180153909-17">Conclusions</hd> <p>Our data show that intestinal symptoms were more prevalent in the ASD group than children in the TD group. The most common intestinal symptom in the children with ASD was constipation, followed by stool smell. These symptoms were significantly more common in both boys and girls with ASD than in the TD children, but there was no significant difference was observed in the prevalence of these symptoms between sexes within the children with ASD. The total scores of ABC, SRS, and CARS, and multiple subscales were significantly higher in children with ASD with constipation, stool smell, and total intestinal symptoms than in those with ASD children without intestinal symptoms, suggesting that intestinal comorbidity might aggravates the core symptoms of children with ASD. Further animal experiments and clinical studies are needed to elucidate the underlying mechanism.</p> <hd id="AN0180153909-18">Acknowledgements</hd> <p>Thank you to all the children and parents who participated in this study. We thank members of the following participating units for their help in data collection and collation: Jun-yan Feng, Qiu Li, Jiang Zhu, Wei Wei, Lin Tian, Jin-zhu Zhao, Ming-yang Zou, Zhao-chuan Yang, Liang Xu, Bo Xiao, Yun Zhang, Tao-tao Jiang, Yan-jun Zhao, and Xi-yue Xiong.</p> <hd id="AN0180153909-19">Author Contribution</hd> <p>TY: conducted data collection and analysis, drafted, and revised the manuscript. TYL and JC: conceived and designed the research, revised the article, and conducted general supervision. QZ, LC, YD, FYJ, YH, LJW, XYK, MJY, JZ, LL, QH, JJC, SFF, YCW, QW, and CHJ: performed data collection, and analysis and interpretation. All authors contributed to the article and approved the submitted version.</p> <hd id="AN0180153909-20">Funding</hd> <p>This work was supported by the National Natural Science Foundation of China (No. 82304119, 82372559, and 81973054), the National Natural Science Foundation of ChongQing (No.CSTB2023NSCQ-BHX0155) and the China Postdoctoral Science Foundation (No.2023M730448).</p> <hd id="AN0180153909-21">Declarations</hd> <p></p> <hd id="AN0180153909-22">Conflict of Interest</hd> <p>The authors declare that there are no conficts of interest relevant to this article.</p> <hd id="AN0180153909-23">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0180153909-24"> <title> References </title> <blist> <bibl id="bib1" idref="ref5" type="bt">1</bibl> <bibtext> Al-Beltagi M. Autism medical comorbidities. 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  Data: Intestinal Symptoms among Children Aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China
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  Data: English
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  Data: <searchLink fieldCode="AR" term="%22Ting+Yang%22">Ting Yang</searchLink><br /><searchLink fieldCode="AR" term="%22Qian+Zhang%22">Qian Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Li+Chen%22">Li Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Ying+Dai%22">Ying Dai</searchLink><br /><searchLink fieldCode="AR" term="%22Fei-Yong+Jia%22">Fei-Yong Jia</searchLink><br /><searchLink fieldCode="AR" term="%22Yan+Hao%22">Yan Hao</searchLink><br /><searchLink fieldCode="AR" term="%22Ling+Li%22">Ling Li</searchLink><br /><searchLink fieldCode="AR" term="%22Jie+Zhang%22">Jie Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Li-Jie+Wu%22">Li-Jie Wu</searchLink><br /><searchLink fieldCode="AR" term="%22Xiao-Yan+Ke%22">Xiao-Yan Ke</searchLink><br /><searchLink fieldCode="AR" term="%22Ming-Ji+Yi%22">Ming-Ji Yi</searchLink><br /><searchLink fieldCode="AR" term="%22Qi+Hong%22">Qi Hong</searchLink><br /><searchLink fieldCode="AR" term="%22Jin-Jin+Chen%22">Jin-Jin Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Shuan-Feng+Fang%22">Shuan-Feng Fang</searchLink><br /><searchLink fieldCode="AR" term="%22Yi-Chao+Wang%22">Yi-Chao Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Qi+Wang%22">Qi Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Chun-Hua+Jin%22">Chun-Hua Jin</searchLink><br /><searchLink fieldCode="AR" term="%22Jie+Chen%22">Jie Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Ting-Yu+Li%22">Ting-Yu Li</searchLink> (ORCID <externalLink term="http://orcid.org/0000-0002-1940-7076">0000-0002-1940-7076</externalLink>)
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  Data: <searchLink fieldCode="SO" term="%22Journal+of+Autism+and+Developmental+Disorders%22"><i>Journal of Autism and Developmental Disorders</i></searchLink>. 2024 54(11):4302-4310.
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  Data: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
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  Data: 9
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  Data: 2024
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  Data: Journal Articles<br />Reports - Research
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  Label: Descriptors
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  Data: <searchLink fieldCode="DE" term="%22Autism+Spectrum+Disorders%22">Autism Spectrum Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms+%28Individual+Disorders%29%22">Symptoms (Individual Disorders)</searchLink><br /><searchLink fieldCode="DE" term="%22Young+Children%22">Young Children</searchLink><br /><searchLink fieldCode="DE" term="%22Physical+Health%22">Physical Health</searchLink><br /><searchLink fieldCode="DE" term="%22Comorbidity%22">Comorbidity</searchLink><br /><searchLink fieldCode="DE" term="%22Foreign+Countries%22">Foreign Countries</searchLink><br /><searchLink fieldCode="DE" term="%22Human+Body%22">Human Body</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22China%22">China</searchLink>
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  Label: Assessment and Survey Identifiers
  Group: Su
  Data: <searchLink fieldCode="SU" term="%22Childhood+Autism+Rating+Scale%22">Childhood Autism Rating Scale</searchLink><br /><searchLink fieldCode="SU" term="%22Social+Responsiveness+Scale%22">Social Responsiveness Scale</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-023-06122-3
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257<br />1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.
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  Data: 2024
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  Data: EJ1442747
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        Value: 10.1007/s10803-023-06122-3
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      – Text: English
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      Pagination:
        PageCount: 9
        StartPage: 4302
    Subjects:
      – SubjectFull: Autism Spectrum Disorders
        Type: general
      – SubjectFull: Symptoms (Individual Disorders)
        Type: general
      – SubjectFull: Young Children
        Type: general
      – SubjectFull: Physical Health
        Type: general
      – SubjectFull: Comorbidity
        Type: general
      – SubjectFull: Foreign Countries
        Type: general
      – SubjectFull: Human Body
        Type: general
      – SubjectFull: China
        Type: general
      – SubjectFull: Childhood Autism Rating Scale
        Type: general
      – SubjectFull: Social Responsiveness Scale
        Type: general
    Titles:
      – TitleFull: Intestinal Symptoms among Children Aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Ting Yang
      – PersonEntity:
          Name:
            NameFull: Qian Zhang
      – PersonEntity:
          Name:
            NameFull: Li Chen
      – PersonEntity:
          Name:
            NameFull: Ying Dai
      – PersonEntity:
          Name:
            NameFull: Fei-Yong Jia
      – PersonEntity:
          Name:
            NameFull: Yan Hao
      – PersonEntity:
          Name:
            NameFull: Ling Li
      – PersonEntity:
          Name:
            NameFull: Jie Zhang
      – PersonEntity:
          Name:
            NameFull: Li-Jie Wu
      – PersonEntity:
          Name:
            NameFull: Xiao-Yan Ke
      – PersonEntity:
          Name:
            NameFull: Ming-Ji Yi
      – PersonEntity:
          Name:
            NameFull: Qi Hong
      – PersonEntity:
          Name:
            NameFull: Jin-Jin Chen
      – PersonEntity:
          Name:
            NameFull: Shuan-Feng Fang
      – PersonEntity:
          Name:
            NameFull: Yi-Chao Wang
      – PersonEntity:
          Name:
            NameFull: Qi Wang
      – PersonEntity:
          Name:
            NameFull: Chun-Hua Jin
      – PersonEntity:
          Name:
            NameFull: Jie Chen
      – PersonEntity:
          Name:
            NameFull: Ting-Yu Li
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 11
              Type: published
              Y: 2024
          Identifiers:
            – Type: issn-print
              Value: 0162-3257
            – Type: issn-electronic
              Value: 1573-3432
          Numbering:
            – Type: volume
              Value: 54
            – Type: issue
              Value: 11
          Titles:
            – TitleFull: Journal of Autism and Developmental Disorders
              Type: main
ResultId 1