INTRODUCTION
Autism spectrum disorder (ASD), a neurodevelopmental condition typically detected in early childhood, manifests with challenges in social engagement, communication, and restricted interests. It affects approximately 1 in 160 children globally (Alamri, 2020). While genetic factors play a significant role in ASD, they alone cannot account for the increasing prevalence, suggesting that environmental influences such as nutrition may contribute (Alamri, 2020). Cognitive impairments, encompassing deficits in both executive and social cognition functions, are well-documented in ASD (Velikonja et al., 2019; Morrison et al., 2020; Hajri et al., 2022).
Recent studies indicate a notable prevalence of motor difficulties in children with ASD, contradicting previous beliefs (Liu, 2013, Liu et al., 2014). While past research using the movement assessment battery for children and test of gross motor development highlighted motor deficits in up to 80% of ASD children (Liu, 2013, Liu et al., 2014), a more recent study revealed that 35% of ASD-diagnosed children under six exhibited motor impairments (Licari et al., 2020). Similarly, studies utilizing tools like The Mullen Scales of Early Learning reported developmental delays in motor skills among toddlers with ASD (Mohd Nordin et al., 2021).
The etiology of ASD remains unclear, with factors such as genetics, environment, nutrition, and immunology implicated (Esparham et al., 2015; Ranjan and Nasser, 2015). Mitochondrial dysfunction, oxidative stress, and nutritional disorders are among the proposed mechanisms (Frye et al. 2013). Early diagnosis and understanding of ASD’s origins are crucial for reducing healthcare costs and enhancing quality of life (Esparham et al., 2015).
ASD is primarily marked by social communication challenges, including poor social reciprocity and delays in verbal and non-verbal communication, along with repetitive behaviors and restricted interests. Although sensory-perceptual and cognitive/behavioral impairments are part of the diagnostic criteria for ASD, motor impairments, despite being common, are not included because they also appear in other developmental disorders like developmental coordination disorder. Cognitive functions in ASD are affected by neuroinflammation, oxidative stress, and disruptions in the gut–brain axis, making treatment for motor and cognitive impairment complex (Al-Mazidi, 2023).
Dietary interventions, particularly elimination diets like gluten-free casein-free (GFCF) diets, have been explored as potential therapies for ASD symptoms, although findings vary (Herbert and Buckley, 2013; Baspinar and Yardimci, 2020). Physical therapists play a significant role in addressing gross motor issues in ASD, often collaborating with occupational therapists (Todhunter-Brown et al., 2014). The evolution of physical therapy approaches from being neurophysiology-based to more eclectic methodologies emphasizes exercise science and motor learning concepts (Scheets et al., 2021; Leech et al., 2022).
Dietary interventions, like the GFCF diet, have been proposed to improve gut microbiota and reduce toxin production, potentially aiding individuals with ASD. The GFCF diet, introduced in the 1980s, involves removing gluten and casein from the diet to prevent autism-like symptoms by influencing brain function. Some studies suggest that this diet reduces proinflammatory responses and improves cognitive and social behaviors in children with ASD. However, there is conflicting evidence on its effectiveness, with some studies showing no impact on autism symptoms (Zafirovski et al., 2024).
Physical therapists focus on improving gross motor abilities, such as walking, mobility, and posture, often working in collaboration with occupational therapists who address upper body functions. Over the past 60 years, the treatment approach for neurological conditions has evolved from a neurophysiology-based method to a more eclectic one that incorporates motor learning principles, exercise science, and biomechanics. This shift was driven by advancements in motor learning and neuroscience. Historically, pediatric physical therapy relied on the neuromaturation theory, which emphasized reducing impairments and promoting developmental milestones through reflex inhibition and developmental sequencing (Todhunter-Brown et al., 2014; Chiarello, 2017; Scheets et al., 2021; Leech et al., 2022).
Incorporating developmental theories like the dynamic, non-linear nature of growth into intervention strategies is essential, along with recognizing the interconnectedness between motor development, social interaction, and communication (Campos et al., 2000; Thelen, 2005; Chiarello, 2017; Lockman and Kahrs, 2017). A recent study revealed significant improvements in gross motor skills compared to the control group. This study suggests that structured physical exercise programs can improve gross motor skills in children with ASD (Castaño et al., 2024). However, despite the common use of physical therapy in ASD management, evidence supporting its efficacy in improving movement skills remains inconclusive (Bhat et al., 2011; Downey and Rapport, 2012).
This study aims to investigate the effects of GFCF diets, specific physical therapy programs, and their combination on the gross motor development and cognitive abilities of children with ASD.
METHODOLOGY
All the procedures of the present randomized control trial have maintained the World Medical Association Declaration of Helsinki for ethical considerations of research. The ethical approval (REC-45/03/797) was obtained from the standing committee for scientific research (HAPO-10-Z.001), Jazan University, Kingdom of Saudi Arabia (KSA). The research team has collected parental consent before starting the study protocol, with all the rights for the participants to withdraw at any time from the procedure.
Participants
All participants were recruited from Prince Turki Bin Nasser Center for Autism in Jazan city, Jazan, KSA. Their chronological age was 4-10 years (Whiteley et al., 2010; Pedersen et al., 2014), diagnosed with ASD based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) criteria at a high-functioning level. The DSM-IV-TR is a handbook that the American Psychiatric Association published that offers standardized criteria for the diagnosis of mental health disorders. It helps clinicians ensure consistent and reliable diagnosis across various settings by including descriptions, symptoms, and other criteria required to diagnose mental disorders. A licensed developmental pediatrician or psychologist interviewed parents regarding the DSM-IV-TR criteria for autism disorder. The 12 DSM-IV-TR criteria that were investigated fell into four categories: social relatedness (which included “impaired non-verbal behavior,” “failure to develop peer relationships,” “lack of seeking to share,” and “lack of social/emotional reciprocity”); communication (which included “delay/lack of speech,” “impaired conversational ability,” “stereotyped/repetitive/idiosyncratic language,” and “lack of make-believe/imitative play”); and restricted/repetitive/stereotyped patterns (which included “stereotyped/restricted patterns of interest,” “non-functional routine or ritual,” “stereotyped or repetitive motor mannerisms,” and “preoccupation with parts of objects”) (Hartley and and Sikora, 2009). All had the ability to follow directions and were classified as level II on gross motor functional classification and had no history of reading disabilities according to parents and caregivers. A multidisciplinary team worked with the autism center in Jazan to evaluate and determine the ASD diagnosis, in addition to a formal diagnosis by the physicians. Participants were excluded if they had any musculoskeletal deformity, gastrointestinal tract disorder, and any metabolic disorder. In addition, children who were using nutritional supplements (vitamins, minerals essential fatty acids, and carnitine) or special diets in the previous 2 months were also excluded.
One hundred children were screened for eligibility, but only 80 of them met the criteria and were randomized based on a simple randomization technique using a shuffled deck of cards into four groups (Suresh, 2011): Group A (n = 20, GFCF diet intervention), Group B (n = 20, physiotherapy intervention), Group C (n = 20, combination between GFCF and physiotherapy intervention), and Group D (n = 20, control group, no study intervention) (Fig. 1) (Knivsberg et al., 2003; Muneer, 2019). All groups had their regular conventional intervention inside the center as they spent the day from 8:00 am to 2:00 pm for full autism care.
Measurement
Measurement of gross motor function skills
The Gross Motor Function Measurement (GMFM) Scale is an observational tool used to evaluate motor function and measure improvements in gross motor ability in five different domains: sitting, crawling and kneeling, walking, running, and leaping (Russell et al., 2000). The ratings vary from 0 to 3, where 0 indicates no task initiation, 1 indicates task initiation (10%), 2 indicates partially completed tasks (10-99%), and 3 indicates 100% task completion. Better gross motor function is indicated by a higher GMFM score. For every dimension, a percentage score is determined. Moreover, the mean of the five-dimension ratings can be used to compute the total score (Russell et al., 2000). The GMFM-66 is a 66-item subset of the original 88 items identified through Rasch analysis; GMFM 88 used for children with ambulatory aids, but GMFM is used with children who are not using orthosis or ambulatory aids (Alotaibi et al., 2014). GMFM 88/66 has high-quality evidence in reliability, internal consistency, and construct validity (Stanford_Binet, n.d.). The physical therapy team of the Prince Turki Bin Nasser Center for autism measured the gross motor skills with the gross motor function measure test (GMFM-66) before the beginning of the intervention and after 3 months of diet and physical therapy program (Vodakova et al., 2022) under the supervision of the research team and following the instruction booklet of GMFM-66.
Measurement of cognitive function
Cognitive abilities were measured using the Stanford–Binet Intelligence Scale, Fifth Edition (SB5). It is an individually administered measure of intelligence and cognitive abilities for persons 2-85 years and older. Yielding not only a full-scale intelligence quotient (IQ) but also a brief IQ, verbal IQ as well as five cognitive factors being tested which are knowledge, quantitative reasoning, visual-spatial processing, working memory, and fluid reasoning, commonly called BINET. The development of the Stanford–Binet scale initiated the modern field of intelligence testing and was one of the first examples of adaptive tests (Pomplun and Custer, 2005). SB5 was administered by certified, research-reliable psychologists. The test was performed with specialist team of the Turki Bin Nasser Center under the supervision of the research team; the test was administered in the presence of the child and his mother; the test administrator, following the instructions given in the test’s instruction booklet, calculated scores for the Stanford–Binet fifth edition. Pomplun and Custer (2005) found a higher correlation of the SB5 verbal and non-verbal working memory subtests with other measures of verbal and non-verbal memory on the same context Baum et al. (2015) found. Most participants obtained higher full-scale IQ scores on the Stanford–Binet, fifth edition, compared to Wechsler Intelligence Scale for Children, fourth edition, with 14% scoring more than one standard deviation higher.
An IQ score was generated from the test results, and different ranges corresponded to different levels of cognitive ability. The standard IQ score ranges for the Stanford–Binet V are examined in depth below:
Low average (80-90): People in this range have cognitive abilities that are marginally lower than those of the general population. Although they could struggle with some academic or difficult problem-solving assignments, they can usually handle everyday issues.
Average (90-109): This is the range that most individuals are in. People in this range usually function well in the majority of academic and professional settings. They are able to understand and solve traditional difficulties since they possess a balanced cognitive ability.
High average (110-119): People in this range have cognitive abilities that are above average. They frequently show exceptional aptitude in a wide range of scholastic subjects and a greater ability to comprehend and solve complicated problems.
High achiever (120-129): Individuals with scores in this range are frequently top achievers with exceptional cognitive skills. They are frequently seen as rapid learners who can manage more difficult mental tasks and have a tendency to perform well in academic environments.
Moderately gifted (130-144): People who are moderately gifted exhibit extraordinary intelligence. They can comprehend and solve extremely complicated problems, and they frequently achieve academic excellence. To keep these people interested and challenged, enrichment or accelerated learning programs could be necessary.
Highly gifted (145-160+): At the very top of the scale, this denotes exceptional intellectual capacity. People who are exceptionally gifted frequently have deep insights and pick up difficult subjects quickly. To fulfill their specific learning needs and to keep them engaged and motivated, they might need special educational accommodations (Janzen et al., 2004; Marusiak and Janzen, 2005; DiStefano and Dombrowski, 2006; Crutcher et al., 2016).
Intervention
GFCF diet
The participants in Groups A and C started to gradually shift their food to be GFCF which includes complete avoidance of foods such as bread, pasta, baked goods, milk, and dairy products. After starting, 1 month of nutritional education in the form of a nutrition education program and nutrition counseling for autistic mothers was conducted for 1 month prior to the experimental study as much as four times (once a week) and every meeting lasted for 2 h, including snack-making tips. The trial extended for 3 months, the first month was for gradual shift and then the next 2 months were completely with the GFCF diet.
Participants were given written instructions about the diet, a 1-h PowerPoint presentation with audio describing the diet, in addition to a 1-h personal consultation with the study team. Mothers were provided with casein-free, gluten-free diet guidebooks. Two guidebooks were developed, one for casein-free diet and another for gluten-free diet which contained information regarding autism, symptoms, and diet studies on casein-free diet and gluten-free diet, how to follow a casein-free and gluten-free diet, lists of allowed and forbidden foods, medications and additives, examples of weekly menus, and additional information, such as points of sale or official websites regarding GFCF products, nutritional recommendations, approaches for healthy lifestyle, and tips for caretakers. However, the family made the final decision about meal plans and their degree of adherence to these guiding principles. The degree of adherence to the guiding principles was self-evaluated (Elder et al., 2006).
Physical therapy
Neurodevelopmental technique (NDT) is a widely used approach in physiotherapy aimed at assessing and treating individuals with neurological conditions. The primary goal of NDT is to promote optimal movement patterns and functional abilities (Zanon et al., 2018). Currently, NDT is described as a client-centered, practical, “problem-solving approach.” It is utilized in the care and treatment of children with central nervous system damage-related impairments of function, mobility, or postural control (Grazziotin Dos Santos et al., 2015). The sensory–motor issues of the patients are not the only issues addressed by the NDT approach. It encompasses all aspects of the person, including the emotional, social, and functional issues that they deal with daily. The NDT technique also addresses developmental issues pertaining to the child, such as deficits in perception and cognition (Kleba, 1984).
After the assessment of gross motor function of each child through the GMFM-66, an individualized physiotherapy program was designed to meet the specific needs of everyone with ASD in Groups B and C.
The intervention program is focused on three main goals:
Help people acquire the motor skills they lack in both static and dynamic environments.
Assist in the development of abilities that improve one’s ability to function independently in the family, peer group, and society.
Lessen the physical limitations brought on by ASD.
Through playful and collaborative exercises that go through the level of developmental level of each child (e.g. trunk-control exercises, sitting, standing groups of exercises, and balance and gait training), encouraging function-oriented movement rather than sensory or stereotypically oriented movement, and improving posture in various daily situations (Holloway and Long, 2019).
Sessions were done on a daily basis for 1 h of handling the child in the department of physiotherapy within the center and giving advice to the parents and caregivers to encourage them to apply the positions and movements throughout the day and on the weekends. Gait training was performed within a great hall designed for that in the center to put an atmosphere of playing and joy. The program was applied for 3 months (Kalisperis et al., 2019).
DATA ANALYSIS
Prior to analysis, the normality of data was checked using the Shapiro–Wilk test. Levene’s test for homogeneity of variances was conducted to test the homogeneity between groups. Data were normally distributed and there was homogeneity of variance. multivariate analysis of variance (MANOVA) test was conducted for comparison of the subject characteristics between groups. Mixed MANOVA was conducted to investigate the effect of treatment on GMFM and the individually administered measure of intelligence and cognitive abilities on BINET. Post-hoc tests using the Bonferroni correction were carried out for subsequent multiple comparison. Data were analyzed based on the intention to treat analysis. Missed post-treatment measures were replaced through the multiple imputation method. The level of significance for all statistical tests was set at P < 0.05. Statistical analysis was performed through the statistical package for social studies (SPSS) version 25 (Chicago, IL) for windows.
RESULTS
Subject characteristics
Table 1 shows the subject characteristics and baseline data of Groups A, B, C, and D. There was no significant difference between groups in age, weight, and height (P > 0.05). Also, there was no significant difference in baseline data of GMFM and BINET between groups (P > 0.05).
Demographic and baseline clinical characteristics of subjects.
Group A | Group B | Group C | Group D | F-value | P-value | |
---|---|---|---|---|---|---|
Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | |||
Age (years) | 6.15 ± 2.01 | 6.20 ± 1.93 | 6.85 ± 2.21 | 6.25 ± 1.86 | 0.53 | 0.66 |
Weight (kg) | 21.80 ± 9.02 | 22.25 ± 7.58 | 25.35 ± 10.72 | 21.20 ± 6.29 | 0.93 | 0.43 |
Height (cm) | 113.35 ± 14.96 | 113.30 ± 14.47 | 120.10 ± 13.96 | 114.60 ± 10.68 | 1.12 | 0.34 |
Sex, N (%) | ||||||
Boys | 14 (70%) | 14 (70%) | 13 (65%) | 14 (70%) | χ2 = 0.17 | 0.98 |
Girls | 6 (30%) | 6 (30%) | 7 (35%) | 6 (30%) | ||
GMFM | 65.85 ± 14.19 | 65.71 ± 11.76 | 66.27 ± 17.74 | 66.14 ± 14.16 | 0.007 | 0.99 |
BINET | 85.90 ± 13.56 | 86.00 ± 13.53 | 90.15 ± 23.89 | 86.25 ± 14.67 | 0.29 | 0.83 |
Abbreviations: BINET, Stanford–Binet V5; GMFM, gross motor function measurement; SD, standard deviation.
Effect of treatment on GMFM and BINET
Mixed MANOVA revealed that there was a significant interaction of treatment and time (F = 10.19, P = 0.001, η 2 = 0.28). There was a significant main effect of time (F = 48.59, P = 0.001, η 2 = 0.56). There was a significant main effect of treatment (F = 2.31, P = 0.03, η 2 = 0.08).
Within-group comparison
There was a significant increase in GMFM (MD = −12.77) and BINET (MD = −14.2) of Group B and a significant increase in GMFM (MD = −14.61) and BINET (MD = −14.55) of Group C post-treatment compared with pretreatment (P < 0.001), while there was no significant change in Group A and Group D (P > 0.05) (Tables 2 and 3).
Clinical characteristics of subjects after intervention.
Outcome | Group A | Group B | Group C | Group D | F-value | P-value | η 2 |
---|---|---|---|---|---|---|---|
Mean ± SD | Mean ± SD | Mean ± SD | Mean ± SD | ||||
GMFM | 66.11 ± 14.88 | 78.48 ± 11.39 | 80.88 ± 14.33 | 65.22 ± 15.22 | 6.76 | 0.001 | 0.21 |
BINET | 86.95 ± 13.48 | 100.20 ± 11.52 | 104.70 ± 21.94 | 88.60 ± 11.96 | 6.44 | 0.001 | 0.20 |
P < 0.05 indicates statistical significance. Abbreviations: BINET, Stanford–Binet V5; η 2, partial eta square; GMFM, gross motor function measurement; P, probability value; SD, standard deviation.
Within groups changes pre- versus post-intervention.
Outcome | Group A | Group B | Group C | Group D | ||||
---|---|---|---|---|---|---|---|---|
MD (95% CI) | P-value | MD (95% CI) | P-value | MD (95% CI) | P-value | MD (95% CI) | P-value | |
GMFM | −0.26 (−4.3, 3.78) | 0.89 | −12.77 (−16.82, −8.74) | 0.001 | −14.61 (−18.66, −10.58) | 0.001 | 0.92 (−3.12, 4.96) | 0.65 |
BINET | −1.05 (−4.37, 2.26) | 0.53 | −14.2 (−17.52, −10.88) | 0.001 | −14.55 (−17.87, −11.23) | 0.001 | −2.35 (−5.67, 0.92) | 0.16 |
P < 0.05 indicates statistical significance. Abbreviations: BINET, Stanford–Binet V5; CI, confidence interval; GMFM, gross motor function measurement; MD, mean difference; P, probability value.
Between-groups comparison
There was a significant increase in GMFM of Group B compared with that of Group A (MD = −12.37, P = 0.03). There was a significant increase in GMFM of Group C compared with that of Group A (MD = −14.47, P = 0.007). There was a significant increase in GMFM of Group B compared with that of Group D (MD = 13.26, P = 0.01). There was a significant increase in GMFM of Group C compared with that of Group D (MD = 15.66, P = 0.004). There was no significant difference in GMFM between Groups A and D and between Groups B and C post-treatment (P > 0.05).
There was a significant increase in BINET of Group B compared with that of Group A (MD = −13.25, P = 0.03). There was a significant increase in BINET of Group C compared with that of Group A (MD = −17.75, P = 0.003). There was a significant increase in BINET of Group C compared with that of Group D (MD = 16.1, P = 0.007). There was no significant difference in BINET between Groups A and D, B and C, and between Groups B and D post-treatment (P > 0.05) (Table 4).
Comparison of post-treatment mean values of GMFM and BINET between groups A, B, C, and D.
GMFM | BINET | |||
---|---|---|---|---|
MD (95% CI) | P-value | MD (95% CI) | P-value | |
Group A vs. group B | −12.37 (−24.05, −0.72) | 0.03 | −13.25 (−25.97, −0.52) | 0.03 |
Group A vs. group C | −14.47 (−26.44, −3.11) | 0.007 | −17.75 (−30.47, −5.02) | 0.003 |
Group A vs. group D | 0.89 (−10.77, 12.55) | 0.99 | −1.65 (−14.37, 11.07) | 0.98 |
Group B vs. group C | −2.4 (−14.06, 9.26) | 0.94 | −4.5 (−17.23, 8.23) | 0.79 |
Group B vs. group D | 13.26 (1.60, 24.93) | 0.01 | 11.6 (−1.13, 24.33) | 0.09 |
Group C vs. group D | 15.66 (4, 27.33) | 0.004 | 16.1 (3.37, 28.83) | 0.007 |
P < 0.05 indicates statistical significance. Abbreviations: BINET, Stanford–Binet V5; CI, confidence interval; GMFM, gross motor function measurement; MD, mean difference; P, probability value.
DISCUSSION
The aim of the study was to evaluate the efficacy of the GFCF diet combined with NDT physical therapy program on gross motor function and cognitive function of children with ASD. The study’s findings indicate significant improvements in gross motor function and cognitive function among children with ASD who received combined physiotherapy and GFCF diet (Group C) and those who received physiotherapy alone (Group B). However, there were no significant changes observed in the group that received the GFCF diet only (Group A) or the control group (Group D).
Comparison between groups revealed that both physiotherapy groups (B and C) demonstrated significant improvements in gross motor function compared to the diet-only group (A) and the control group (D). Similar findings were observed in cognitive function, except for a non-significant difference between Group B and the control group (D).
The lack of significant improvement in gross motor function and cognitive function in the diet-only group (A) may be attributed to the short duration of the trial, as suggested by Johnson et al. (2011) and Knivsberg et al. (1995). In contrast, Millward et al. (2008) reported significant improvements in behavior with a longer dietary intervention period, indicating potential limitations of the current study’s duration (Campos et al., 2000; Bhat et al., 2011; Lockman and Kahrs, 2017).
The impact of GFCF dietary intervention on ASD behaviors and development remains unclear, with Whiteley et al. (2013) suggesting multiple dietary effect models depending on individual variability in symptom presentation (Downey and Rapport, 2012).
Physiotherapy alone (Group B) significantly improved gross motor function, potentially due to enhancements in balance and coordination. This aligns with findings from Castaño et al. (2023) and Najafabadi et al. (2018), supporting structured physical activity interventions for ASD (Whiteley et al., 2010; Pedersen et al., 2014).
The observational tool used to evaluate motor function GMFM and its applicability beyond typical age ranges, as demonstrated by Vodakova et al. (2022), underscores the effectiveness of physiotherapy interventions in improving motor function (Suresh, 2011).
Physical activity interventions have shown positive effects on motor competence in children without ASD, as evidenced by Utesch et al. (2019). Similarly, Reinders et al. (2019) highlighted the importance of physical activity for individuals with ASD, correlating social functioning with physical activity levels (Knivsberg et al., 2003; Muneer, 2019).
Teixeira (Vodakova et al., 2022) suggested sports participation as a therapeutic strategy for ASD individuals, emphasizing its potential benefits on motor abilities and executive functions. Neurodevelopmental physiotherapy programs incorporating visual, auditory, tactile, and proprioceptive stimulation may enhance gross motor function (Russell et al., 2000).
Group B also demonstrated significant improvement in cognitive function, possibly linked to improved gross motor function. Monteiro et al. (2022b) suggested that executive function deficiencies may impact cognitive function in ASD individuals (Pomplun and Custer, 2005).
The combination of GFCF diet and physiotherapy (Group C) yielded the most significant improvements in both gross motor and cognitive functions. This may be attributed to the cumulative effects of both interventions, supported by Pennesi and Klein (2012) who reported fewer autism symptoms with the GFCF diet. Additionally, the belief effect and potential ergogenic effects of the GFCF diet may have contributed to the observed improvements (Janzen et al., 2004; Marusiak and Janzen, 2005; Crutcher et al., 2016).
In conclusion, while physiotherapy alone and in combination with the GFCF diet showed significant improvements in gross motor and cognitive functions among children with ASD, the GFCF diet alone did not produce significant changes within the study’s timeframe. The study underscores the importance of comprehensive intervention approaches tailored to individual needs in ASD management.
Study limitations
It will be recommended to conduct a similar study with long-term effect not less than 6 to 12 months as the period of 3 months only was a limitation of the current study. Also, the adherence with the children with ASD for the complete conversion of their diet to GFCF was self-evaluated which might affect the results and should be treated in future trials. This study did not focus on blinding which made it necessary to be focused on future research for the same issue.
CONCLUSION
Gross motor development on GMFM and cognitive function on BINET SB5 of children with ASD significantly improved with the combination of GFCF diet and individualized neurodevelopmental physical therapy program. Also, neurodevelopmental physical therapy improves the level of gross motor development and cognitive function of ASD children, whereas using GFCF diet alone had no change when the diet and NDT physiotherapy were applied for three consecutive months.