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To determine whether a gluten-free diet (GFD) compared with a gluten-containing diet (GD) influences functioning of children with autism spectrum disorders (ASD), we performed a randomized, controlled, single-blinded trial. Sixty-six children (36–69 months) with ASD, within the normal IQ (> 70) range, who had been on a GFD for at least 8 weeks before enrollment were eligible for inclusion. After an 8-week run-in period on a GFD, the GFD group continued this diet and the GD group consumed at least one normal meal containing gluten per day for 6 months. There were no differences between groups in autistic symptoms, maladaptive behaviors, or intellectual abilities after the intervention. A GFD compared with a GD did not affect functioning of children with ASD. Trial registration ClinicalTrials.gov, number NCT02280746.
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Vol:.(1234567890)
Journal of Autism and Developmental Disorders (2020) 50:482–490
https://doi.org/10.1007/s10803-019-04266-9
1 3
ORIGINAL PAPER
Gluten‑Free Diet inChildren withAutism Spectrum Disorders:
ARandomized, Controlled, Single‑Blinded Trial
AnnaPiwowarczyk1· AndreaHorvath2· EwaPisula3· RafałKawa3· HaniaSzajewska2
Published online: 28 October 2019
© Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
To determine whether a gluten-free diet (GFD) compared with a gluten-containing diet (GD) influences functioning of
children with autism spectrum disorders (ASD), we performed a randomized, controlled, single-blinded trial. Sixty-six
children (36–69months) with ASD, within the normal IQ (> 70) range, who had been on a GFD for at least 8weeks before
enrollment were eligible for inclusion. After an 8-week run-in period on a GFD, the GFD group continued this diet and the
GD group consumed at least one normal meal containing gluten per day for 6months. There were no differences between
groups in autistic symptoms, maladaptive behaviors, or intellectual abilities after the intervention. A GFD compared with a
GD did not affect functioning of children with ASD.
Trial registration ClinicalTrials.gov, number NCT02280746.
Keywords Randomized controlled trial· Autism spectrum disorder· Children· Gluten
The gluten-free and/or casein-free (GFCF) diet addresses
the hypothesis that children with autism spectrum disorders
(ASD) absorb peptides as a result of a leaky gut (Whiteley
etal. 1999), thus, use of a GFCF diet may ameliorate behav-
ioral symptoms. Excessive activity of peptides derived from
the metabolism of gluten and casein (Israngkun etal. 1986;
Shattock and Whiteley 2002; Christison and Ivany 2006) is
thought to impair neurotransmission (Knivsberg etal. 1995).
However, data on the efficacy of a GFCF diet as a treat-
ment for ASD in children are limited. Our 2018 systematic
review identified 6 relevant randomized controlled trials
(RCTs) (214 participants) (Piwowarczyk etal. 2018). With
few exceptions, there were no significant differences in ASD
core symptoms between groups, as measured by standard-
ized scales. The remaining differences, if present, referred to
parent-based assessment tools or other developmental/ASD-
related features. We concluded that, overall, there is little
evidence that a GFCF diet is beneficial for the symptoms of
ASD in children. However, methodological limitations in the
included trials may invalidate the results. Furthermore, 4 of
6 of these trials compared a GFCF diet with a “regular” diet
(presumably gluten-containing as there was no reporting on
no specific effort to ensure gluten was consumed) and few
trials included a GFD or GFCF diet run-in/washout period.
Data on the effects of a gluten-free diet (GFD) only are
even more limited. Despite such uncertainty, avoidance of
gluten, initiated by caregivers or clinicians, in preschool
children with ASD is highly prevalent (Rubenstein etal.
2018). Only one previous trial has investigated the effects
of a GFD on gastrointestinal (GI) symptoms and behavio-
ral indices in children with ASD, with results suggesting
that gluten elimination affects these outcomes (Ghalichi
etal. 2016). However, this trial compared a GFD with a
“regular” diet and did not include a GFD run-in period. We,
therefore, aimed to further assess the effect of gluten on the
functioning of children with ASD by comparing use of a
GFD and gluten-containing diet (GD). In accordance with
guidelines (National Institute for Health and Clinical Excel-
lence 2009), each child receiving the GD diet consumed
some gluten-containing foods (e.g., bread, chapattis, pasta,
biscuits, or cakes) in more than one meal every day. In real
* Hania Szajewska
hania@ipgate.pl
1 Department ofPaediatrics withClinical Assessment Unit,
The Medical University ofWarsaw, Zwirki i Wigury 63a,
02-091Warsaw, Poland
2 Department ofPaediatrics, The Medical University
ofWarsaw, Zwirki i Wigury 63A, 02-091Warsaw, Poland
3 Department ofHealth andRehabilitation Psychology,
Faculty ofPsychology, University ofWarsaw, Stawki 5/7,
00-183Warsaw, Poland
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... The year in which the most articles were published was 2019 (n = 4) [33,40,41,44], followed by 2020 (n = 3) [35,37,45], 2021 (n = 2) [32,38], 2017 (n = 2) [34,39], 2018 (n = 2) [43,46], 2022 (n = 1) [42] and 2023 (n = 1) [36]. Nine of the included studies were randomised clinical trials [32,33,[36][37][38]41,42,44,46], and six [34,35,39,40,43,45] were a non-randomized clinical trial (Table 2). Nutrients 2023, 15, x FOR PEER REVIEW 5 of 19 Figure 1. ...
... Most of the studies (n = 4) were conducted in the United States [33][34][35][36]. The remaining studies were conducted in different countries such as Iran (n = 2) [37,38], Japan (n = 2) [39,40], Spain (n = 2) [41,42], United Kingdom (n = 1) [43], Poland (n = 1) [44], China (n = 1) [45], Iceland (n = 1) [32] and Korea (n = 1) [46] ( Table 2). The year in which the most articles were published was 2019 (n = 4) [33,40,41,44], followed by 2020 (n = 3) [35,37,45], 2021 (n = 2) [32,38], 2017 (n = 2) [34,39], 2018 (n = 2) [43,46], 2022 (n = 1) [42] and 2023 (n = 1) [36]. ...
... The remaining studies were conducted in different countries such as Iran (n = 2) [37,38], Japan (n = 2) [39,40], Spain (n = 2) [41,42], United Kingdom (n = 1) [43], Poland (n = 1) [44], China (n = 1) [45], Iceland (n = 1) [32] and Korea (n = 1) [46] ( Table 2). The year in which the most articles were published was 2019 (n = 4) [33,40,41,44], followed by 2020 (n = 3) [35,37,45], 2021 (n = 2) [32,38], 2017 (n = 2) [34,39], 2018 (n = 2) [43,46], 2022 (n = 1) [42] and 2023 (n = 1) [36]. Nine of the included studies were randomised clinical trials [32,33,[36][37][38]41,42,44,46], and six [34,35,39,40,43,45] were a non-randomized clinical trial (Table 2). ...
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... Of those, 15 clinical trials met the inclusion and exclusion criteria and were selected for the present systematic review. In specific, six studies evaluated the efficacy of a low-FODMAP diet [36][37][38][39][40][41][42], five evaluated the efficacy of FRD/LRD [28,[43][44][45][46], three trials evaluated the efficacy of the GFD [47][48][49], and one evaluated the efficacy of the MD [50]. The flowchart of the eligible studies is shown in Figure 1. ...
... Currently, three trials have been published investigating the effects of the GFD on FGIDs in the pediatric population [47][48][49]. Two studies were RCTs [48,49], and one was a double-blind placebo-controlled clinical trial [47]. ...
... Currently, three trials have been published investigating the effects of the GFD on FGIDs in the pediatric population [47][48][49]. Two studies were RCTs [48,49], and one was a double-blind placebo-controlled clinical trial [47]. Two studies [44,47] assessed the role of GFD in GI outcomes in children with several FGIDs, and one study [48] was on children with FAP/FC. ...
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Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focuses on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the gluten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and functional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and single-arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, and GFD have no place in daily clinical practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may experience some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data suggest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.
... Of those, 15 clinical trials met the inclusion and exclusion criteria and were selected for the present systematic review. In specific, 6 studies evaluated the efficacy of a low-FODMAP diet [36][37][38][39][40][41][42], 5 the efficacy of FRD/LRD [28,[43][44][45][46], 3 trials the efficacy of the GFD [47][48][49] and 1 the efficacy of the MD [50]. The flowchart is shown in Figure 1. ...
... Currently, 3 trials have been published investigating the effects of the GFD on FGIDs in the pediatric population [47][48][49]. Two studies were RCTs [48,49] and 1 was a double-blind placebo controlled clinical trial [47]. ...
... Currently, 3 trials have been published investigating the effects of the GFD on FGIDs in the pediatric population [47][48][49]. Two studies were RCTs [48,49] and 1 was a double-blind placebo controlled clinical trial [47]. Two studies [44,47] assessed the role of GFD on GI outcomes in children with several FGIDs and 1 study [48] on children with FAP/FC. ...
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Full-text available
Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focus-es on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the glu-ten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and func-tional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and sin-gle arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, or GFD have no place in daily practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may have some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data sug-gest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.
... All eleven trials were described as randomized, although the method of randomisation was not reported for any trial. Four trials were double-blind (Elder et al., 2006;Hyman et al., 2016;Navarro et al., 2015;Pusponegoro et al., 2015), and five were single-blind (Ghalichi et al., 2016;Johnson et al., 2011;Knivsberg et al., 2002;Piwowarczyk et al., 2020;Whiteley et al., 2010). Two trials did not report information regarding the blinding process (El-Rashidy et al., 2017;González-Domenech et al., 2020). ...
... In general, samples were small. In six studies, the sample analysed was between 13 and 29 participants (Elder et al., 2006;González-Domenech et al., 2020;Hyman et al., 2016;Johnson et al., 2011;Knivsberg et al., 2002;Navarro et al., 2015;), while five had a somewhat larger sample of 40 (El-Rashidy et al., 2017), 47 (Pusponegoro et al., 2015), 55 (Whiteley et al., 2010), 58 (Piwowarczyk et al., 2020) or 76 participants (Ghalichi et al., 2016). The ages of participating children ranged from 2 to 18 years with most studies focused on younger children (e.g. ...
... There was no significant difference in mean autism index score for the RD group (79.92 ± 15.49 vs. 80.92 ± 16.24; p = 0.12). Results from recent trials also confirm the absence of improvement in autistic symptoms, maladaptive behaviours, or intellectual abilities (Piwowarczyk et al., 2020), as well as behavioural symptoms (González-Domenech et al., 2020) when consuming GFCF diet compared to a normal diet. ...
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Objectives The purpose of this review was to systematically search and critically analyse literature concerning the efficacy of gluten-free and/or casein-free diets in treating maladaptive behaviours in children with autism spectrum disorder. Methods Eleven randomized clinical trials retrieved from PubMed and Cochrane Library databases and hand search were reviewed and assessed for methodological quality using the Cochrane Collaboration’s risk of bias tool. Results Samples were mostly small, and few studies yielded evidence of statistically significant behavioural outcomes attributable to dietary interventions. Conclusions The results of this review imply that the efficacy of gluten-free and/or casein-free diets for individuals with autism spectrum disorder remains unsubstantiated. Larger and better designed studies focused on specific outcomes, and which are not dependent on unblinded researcher or parent report, are needed to establish whether gluten-free and/or casein-free diets are effective for children with autism spectrum disorder or any subgroup of such children. Systematic Review Registration PROSPERO CRD42020142407.
... There is no evidence either against or in favour of gluten avoidance for managing symptoms of ASD in children. Nonetheless, there are GFCF celebrities to endorse such a cause [60]. ...
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... Існують дослідження, що доводять певну ефективність дієт у полегшенні симптомів ШКТ у дітей з РАС: мета-аналіз показав, що безглютенова та безказеїнова (БГБК) дієта може зменшити стереотипну поведінку та покращити когніти-вні здібності дітей з аутизмом [19]. Але на сьогоднішній день немає єдиної згоди щодо механізму впливу БГБК дієт та мало доказів сприятливого впливу БГБК дієт на симптоми РАС [20]. Тому ефективність і безпека БГБК дієт при аутизмі залишаються суперечливими: низка досліджень повідомила про відсутність суттєвих змін у симптомах РАС, що ставить під сумнів корисні ефекти дієти БГБК. ...
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... Regarding the studies with casein and gluten exclusion diets (Table I), five studies were found with populations that vary in: sample size, origin, age group, timing of the intervention and symptom assessment scales. When evaluating the smaller studies (6 and 8 weeks) (14,15), a gluten-free diet (GFD) was considered in the Iranian and Polish population, obtaining improvements in stereotyped behavior, communication and social interaction, as well as in the scores of the instruments: ADO-2, SCQ and ASRS, respectively. Regarding interventions that con- sider both the GFD and the Casein-Free Diet (CFD), 12-month interventions are observed in children under 18 years of age, obtaining improvements in the symptomatology appreciated by the CARS and ABC post-intervention psychometric tools (16,17). ...
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Chapter
Autism spectrum disorders (ASD) are complex neurobehavioral conditions with varied phenotypes involving multiple organ systems. Gastrointestinal (GI) manifestations are widely reported among children with ASD. Due to sensory and communicative limitations inherent to ASD, GI conditions may present atypically resulting in diagnostic challenges. Substantial gaps exist in the current understanding of the pathophysiology of ASD and their close link with GI comorbidities. Further understanding of these links may lead to the creation of novel therapies for this population. Here, we review the prevalence, pathophysiology, diagnosis, and management of GI disease in children with ASD.
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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear etiology, and due to the lack of effective treatment, ASD patients bring enormous economic and psychological burden to families and society. In recent years, many studies have found that children with ASD are associated with gastrointestinal diseases, and the composition of intestinal microbiota (GM) is different from that of typical developing children. Thus, many researchers believe that the gut-brain axis may play an important role in the occurrence and development of ASD. Indeed, some clinical trials and animal studies have reported changes in neurological function, behavior, and comorbid symptoms of autistic children after rebalancing the composition of the GM through the use of antibiotics, prebiotics, and probiotics or microbiota transfer therapy (MMT). In view of the emergence of new therapies based on the modulation of GM, characterizing the individual gut bacterial profile evaluating the effectiveness of intervention therapies could help provide a better quality of life for subjects with ASD. This article reviews current studies on interventions to rebalance the GM in children with ASD. The results showed that Lactobacillus plantarum may be an effective strain for the probiotic treatment of ASD. However, the greater effectiveness of MMT treatment suggests that it may be more important to pay attention to the overall balance of the patient’s GM. Based on these findings, a more thorough assessment of the GM is expected to contribute to personalized microbial intervention, which can be used as a supplementary treatment for ASD.
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Lay summary: Gluten free diets (GFDs) are commonly used as an alternative therapy for autism spectrum disorder (ASD); however, the effectiveness is still uncertain which makes it important to know who tries this type of diet. We found that one in five preschool aged children with ASD had ever used a GFD. Children with gastrointestinal conditions and developmental regression were more likely to have tried a GFD.
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Myszkowska-Ryciak J, Harton A, Gajewska D. Analiza wartości odżywczej i kosztów diety bezglutenowej w porównaniu do standardowej racji pokarmowej. Med Og Nauk Zdr. 2015; 21(3): 312–316. Streszczenie Wprowadzenie. Dieta bezglutenowa jest podstawową metodą postępowania terapeutycznego w celiakii. Pacjent, stojąc przed koniecznością wyeliminowania glutenu z diety, teoretycznie może wybierać pomiędzy produktami naturalnie bez-glutenowymi lub produktami bezglutenowymi specjalnego przeznaczenia żywieniowego. Pomimo dobrej dostępności produktów bezglutenowych wciąż istnieją problemy związane ze zbilansowaniem takiej diety, jak również jej kosztem. Cel. Celem pracy była ocena zawartości wybranych składników pokarmowych oraz oszacowanie kosztów diety bezglu-tenowej z wykorzystaniem dostępnych na polskim rynku produktów naturalnie bezglutenowych oraz bezglutenowych środków spożywczych specjalnego przeznaczenia żywieniowego w odniesieniu do diety zwyczajowej. Materiał i metody. Do analizy wybrano całodzienną modelową rację pokarmową na poziomie 2000 kcal, którą następnie zmodyfikowano pod kątem zamiany produktów zbożowych na produkty naturalnie bezglutenowe oraz bezglutenowe środki spożywcze zgodnie z założeniami diety bezglutenowej. Oceniono zawartość wybranych składników pokarmowych dostarczanych przez produkty zbożowe tradycyjne oraz ich bezglutenowe zamienniki. Analizy kosztów racji pokarmowych dokonano w oparciu o cenniki firm oferujących produkty bezglutenowe oraz uśrednione ceny produktów spożywczych z warszawskich supermarketów. Wyniki. Wykazano, że koszt bezglutenowej racji pokarmowej przy założeniu wyłącznie zamiany tradycyjnych produktów zbożowych wzrasta o prawie 30%. Przy podobnej ilości energii oraz węglowodanów ogółem, bezglutenowe zamienniki produktów zbożowych wnoszą do racji pokarmowej zdecydowanie mniejszą wartość odżywczą w odniesieniu do białka, żelaza, cynku, magnezu, tiaminy oraz błonnika pokarmowego przy jednoczesnej wyższej zawartości tłuszczu. Wnioski. Dostępne w handlu produkty bezglutenowe są znacznie droższe od odpowiadających im glutenowych produktów tradycyjnych. Zamiana produktów tradycyjnych na ich bezglutenowe odpowiedniki powoduje istotne obniżenie wartości odżywczej diety.
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In pediatric settings, parents often raise concerns about possible gastrointestinal (GI) symptoms in autism spectrum disorder (ASD), yet the specificity of these concerns are not well studied. To conduct a meta-analysis of research investigating GI symptoms among children with ASD. We searched Medline, PsycINFO, and PubMed databases (1980-2012) in peer-reviewed journals. Analysis involved studies with a comparison group presenting quantitative data on GI symptoms using combinations of terms for ASD and GI indicators. The systematic search yielded 15 studies. We calculated effect sizes and 95% confidence intervals (CIs) using a random-effects model. Children with ASD experience significantly more general GI symptoms than comparison groups, with a standardized mean difference of 0.82 (0.24) and a corresponding odds ratio (OR) of 4.42 (95% CI, 1.90-10.28). Analysis also indicated higher rates of diarrhea (OR, 3.63; 95% CI, 1.82-7.23), constipation (OR, 3.86; 95% CI, 2.23-6.71), and abdominal pain (OR, 2.45; 95% CI, 1.19-5.07). Results indicate greater prevalence of GI symptoms among children with ASD compared with control children. Identified studies involved high methodological variability and lack of comprehensive data prohibited analysis of GI pathophysiologies (eg, gastroesophageal reflux) typically associated with organic etiologies, limiting conclusions about the underpinnings of the observed association. Future research must address critical questions about the causes and long-term impact of GI symptoms in ASD. Such analyses will require more systematic research and clinical activities, including improved diagnostic screening, standardized assessment, and exploration of potential moderators (eg, dietary restrictions).
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Objectives: To examine the nutritional quality of gluten-free (GF) products specifically marketed for children. Methods: All child-targeted food products were purchased from 2 major supermarket chains in Calgary, Alberta, Canada. Using the Pan American Health Organization Nutrient Profile Model, the nutritional quality of products with a GF claim was compared with those without such a claim. A secondary analysis further compared the nutrient profile of child-targeted GF products to their product "equivalents." Results: Overall, child-targeted GF products had lower levels of sodium, total fat, and saturated fat but also had less protein and a similar percentage of calories from sugar compared with child-targeted products without a GF claim. According to the Pan American Health Organization criteria, both GF products and "regular" products designed for children can be classified as having poor nutritional quality (88% vs 97%; P < .001). When analyzed in light of their product equivalents without a GF claim, both had similarly high levels of sugar (79% vs 81%; P < .001). Conclusions: GF supermarket foods that are targeted at children are not nutritionally superior to regular child-targeted foods and may be of greater potential concern because of their sugar content. The health halo often attributed to the GF label is not warranted, and parents who substitute GF products for their product equivalents (assuming GF products to be healthier) are mistaken. Parents of children with gluten intolerance and/or sensitivity, along with parents who purchase GF products for other health reasons, need to carefully assess product labels when making purchases.
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Background Genetic and environmental factors are both responsible for the etiology of autism spectrum disorders (ASD). Although epidemiological studies have been conducted to clarify the association between restriction diets and ASD, the conclusion remains unclear. This study was undertaken to investigate the effect of gluten free diet (GFD) on gastrointestinal symptoms and behavioral indices in children with ASD. Methods In this randomized clinical trial, 80 children diagnosed with ASD by the Autism Diagnostic Interview-Revised (ADI-R) were assigned into GFD (n=40) and regular diet (RD) (n=40) groups for 6 weeks. At the beginning and end of the intervention, the ROME Ш questionnaire for evaluating gastrointestinal symptoms and Gilliam Autism Rating Scale 2 questionnaire (GARS-2) for assessing psychometric properties were completed. Results Of the 80 children, 53.9% had gastrointestinal abnormalities. In the GFD group, the prevalence of gastrointestinal symptoms decreased significantly (P<0.05) after intake of GFD (40.57% vs. 17.10%) but increased insignificantly in the RD group (42.45% vs. 44.05%). GFD intervention resulted in a significant decrease in behavioral disorders (80.03±14.07 vs. 75.82±15.37, P<0.05) but an insignificant increase in the RD group (79.92±15.49 vs. 80.92±16.24). Conclusion This study suggested that GFD may be effective in controlling gastrointestinal symptoms and ASD behaviors.
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Background: Gastrointestinal (GI) symptoms are frequently reported in children with Autism Spectrum Disorder (ASD), and an impact of GI comorbidity on ASD behavioral problems has been hypothesized. Aims: To explore the type and the prevalence of GI symptoms in ASD patients and typical development (TD) controls, and to investigate their possible association with behavioral problems. Methods: A total of 230 preschoolers were included in this study. Specifically, four groups of children were evaluated: ASD individuals suffering from GI symptoms (ASD/GI+), ASD subjects without GI symptoms (ASD/GI-), TD peers with (TD/GI+) and without (TD/GI-) GI symptoms. Parental report of behavioral problems and GI symptoms were assessed through the Child Behavior Check List 1½-5. Results: A significant higher percentage of ASD (37.4%) versus TD (14.8%) with GI symptoms was observed. 'Constipated' and 'Not-Eat' were the most frequent GI symptoms both in ASD and in TD groups, but they were evaluated as more severe in ASD patients. ASD/GI+ children had more anxiety problems, somatic complaints, externalizing and total problems than ASD/GI- individuals. TD/GI+ did not show more behavioral problems than TD/GI-. Conclusion: Development of evidence-based guidelines for identification of GI problems in ASD preschoolers is warranted. GI symptomatology should be accurately assessed, especially in ASD children with anxiety and/or externalizing behavioral problems.