Abstract

Background: Autism was once thought to be an uncommon developmental disorder, but recent studies have reported increased prevalence and the condition is now thought to occur in at least 1% of children. It is being identified in increasing numbers in Bangladesh. In a study conducted by WHO and National Institute of Mental Health the prevalence of Autism is found to be 8 per 1000 in Bangladesh.

Objective: To find out the development in behavior of children with ASD.

Methods: This Randomized control trial study among the patient attending in Department of Psychiatry, National Institute of Mental Health & Hospital, Dhaka, Bangladesh. The study was carried out 6 months from Januaruy, 2019 to Jun, 2019. A total of 40 children (6 years or under 6 years) having Autism Spectrum Disorders (ASD), that of randomly selected (lottery method) 20 children received a specific dietary intervention was considered as group I and 20 children who not received a specific dietary intervention was considered as group II, who came in the MTW (More than word) clinic were included in this study. Children having Autism Spectrum Disorder (ASD) of both sexes who were 6 years old and below.

Results: Behavioral domains of children with ASD are the main outcome variables. Autism Spectrum Disorders was more common in male children, where male to female ratio was 5.7:1 in group I and 19:1 in group II and 9:1 in the whole study patients. Most of the patients came from Dhaka district in both groups, which was 16(80.0%) in group I and 18(90.0%) in group II. No schooling patients was found 14(70.0%) in group I and 13(65.0%) in group II. Patients had previous medical help was found 16(80.0%) in group I and 17(85.0%) in group II. Most of the parents were master degree pass in both groups. Eighty percent (80.0%) in group I and 15(75.0%) in group II patients came from upper (20,000->50,000 tk) income group family. The mean post social relationship was 3.67±0.47 in group I and 3.87±0.51 in group II. Mean pre per interaction was found 2.43±0.53 in group I and 2.28±0.48 in group II. The mean post peer interaction was 3.25±0.60 in group I and 3.29±0.53 in group II. Mean pre communication was found 2.58±0.61 in group I and 2.12±0.77 in group II. Mean post communication was found 3.77±0.61 in group I and 3.65±0.68 in group II. Mean pre sensory a response was found 2.82±0.59 in group I and 2.96±0.75 in group II. The mean post sensory responses was found 3.58±0.55 in group I and 3.64±0.48 in group II. All specific behaviors were significantly (p<0.05) improved within the groups from pre to post intervention period, but no significant (p>0.05) difference were found between the groups during post intervention period.

Conclusion: The improvements in behavior of children with ASD were almost similar between two groups.

Introduction

Autism was once thought to be an uncommon developmental disorder, but recent studies have reported increased prevalence and the condition is now thought to occur in at least 1% of children.^1,2,3,5 It is being identified in increasing numbers in Bangladesh.⁶ In a study conducted by WHO and National Institute of Mental Health the prevalence of Autism is found to be 8 per 1000 in Bangladesh.⁷ No single cause has been established yet, although genetic and environmental factors are implicated. A number of risk factors being investigated include genetic, infectious, metabolic, nutritional and environmental, but less than 10 to 12% of cases specific causes have found.⁸ Simultaneously the use of alternative treatment approaches in children with autism has increased, but due to significant methodological flaws, the currently available data are inadequate to guide treatment recommendations.⁹ In practice, treatment of ASD usually consists of a comprehensive program of educational intervention, speech therapy, behavioral treatment and developmental therapies. The popularity of these diets indicate a need for more in-depth and rigorous research into their efficacy. There is growing evidence that nutritional therapy can really make a big difference to children with autism. Many have severely disrupted digestion, so a major focus must be restoring balance their blood sugar, check for brain-polluting heavy metals, exclude food additives, identify food allergies and possible nutrient deficiencies, and ensure an optimal intake of essential fats. A popular belief that specific dietary changes can improve the symptoms of children with autism. The effectiveness of elimination diets in improving the behavior of children with autism has only recently been scientifically researched.¹⁰ A gluten-free diet is often used for children with autism in combination with a casein-free diet. Both diets are called elimination diets because a particular type of food is eliminated from the child's meals and snacks.¹¹ one well-controlled study focused on children with autism who had abnormally high protein by-products in their urine, and therefore were more likely to be sensitive to casein and gluten. One group of these children was fed a strict casein- and gluten-free diet for 12 months. This group had significantly fewer autistic symptoms than the remaining children, who were not fed this diet.¹² Another well-controlled study reported no significant improvements in speech for 13 children who followed a gluten-free casein-free diet for 6 weeks.¹³ Sucrose or aspartame also affects behavior and cognitive performance in children.¹⁴ There is some evidence that the ketogenic diet may be used in autistic behavior as an additional or alternative therapy¹⁵ .The popularity of these diets indicates a need for more in-depth and rigorous research into their efficacy. Mulloy et al.¹⁶ systematically reviewed research on the effects of gluten-free and/or casein-free (GFCF) diets in the treatment of ASD. Jyonouchi et al.¹⁷ study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children.

Materials and Methods

This randomized control trial (RCT) study among the patient attending in Department of Psychiatry, National Institute of Mental Health & Hospital, Dhaka, Bangladesh. The study was carried out 6 months from Januaruy, 2019 to Jun, 2019. A total of 40 children (6 years or under 6 years) having Autism Spectrum Disorders (ASD), that of randomly selected (lottery method) 20 children received a specific dietary intervention was considered as group I and 20 children who not received a specific dietary intervention was considered as group II, who came in the MTW (More than word) clinic were included in this study.Children having Autism Spectrum Disorder (ASD) of both sexes who were 6 years old and below.In the first group behavior of the children who received a dietary intervention at the beginning of the program and followed up for a period of 6 months (group I). In the second group who didn't not receive a dietary intervention were also followed up for 6 months ((group II). Other treatments were same in both groups. Behavior of the children in both groups were measured by an Autism specific clinical interview questionnaire called PIA-CV at the beginning and at the end of the intervention period.

Data Analysis: Statistical analyses were carried out by using the Statistical Package for Social Sciences version 16.0 for Windows (SPSS Inc., Chicago, Illinois, USA). The mean values were calculated for continuous variables. The quantitative observations were indicated by frequencies and percentages. Chi-Square test with Yates correction was used to analyze the categorical variables, shown with cross tabulation. Student t-test was used for continuous variables. P values <0.05 was considered as statistically significant.

Results

Table .1 shows sex distribution of the study patients, male were predominant in both groups, which was 17(85.0%) in group I and 19(95.0%) in group II. The difference was not statistically significant (p>0.05) between two groups. This study was includes ASD children (median age 4.8 years) on the unrestricted (n=100) or elimination (n=77) diet appropriate with their immune reactivity. Group l: Children who have received a dietary intervention Group Il-Children who have not received a dietary intervention. Controls include children with non-allergic food hypersensitivity (NFH: median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13).

Ns=not significant.

P value reached from fisher's exact test.

Ns=not significant.

P value reached from fisher's exact test.

(Table 2) shows residence of the study patients, it was observed that majority patients were came from Dhaka district in both groups, which was 16(80.0%) in group I and 18(90.0%) in group II. The difference was not statistically significant (p>0.05) between two groups.

Ns=not significant.

P value reached from fisher's exact test.

(Table 3) shows schooling of the study patients, it was observed that no schooling patients was found 14(70.0%) in group I and 13(65.0%) in group II. Formal schooling was found 4(20.0%) in group I and 5(25.0%) in group II. The difference was not statistically significant (p>0.05) between two groups.

Ns=not significant.

P value reached from fisher's exact test.

(Table 4) shows mode of delivery of the study patients, it was observed that majority patients had caesarean section in both groups, which was 16(80.0%) in group I and 15(75.0%) in group II. The difference was not statistically significant (p>0.05) between two groups.

(Table 5) shows birth history of the study patient's, it was observed that majority patient's birth history was uneventful in both groups, which was 18 (90.0%) in group I and 17 (85.0%) in group II. The difference was not statistically significant (p>0.05) between two groups.

Ns=not significant.

P value reached from fisher's exact test.

(Table 6) shows mild stone of development of the study patients, it was observed that age appropriate was found 19(95.0%) in group I and 20(100.0%) in group II. The difference was not statistically significant (p>0.05) between two groups.

Ns=not significant.

P value reached from fisher's exact test.

(Table 7) shows previous medical help of the study patients, it was observed that patients had previous medical help was found 16(80.0%) in group I and 17(85.0%) in group

(Table 8) shows Most of the fathers were masters pass education in both groups, which was 13(65.0%) in group I and 17(85.0%) in group II. Majority 11(55.0%) fathers were service holder in group I and 5(25.0%) in group II. Most 14(70.0%) mothers were masters pass education level in group I and 15(75.0%) in group II. Majority mothers were professional occupations. Most (80.0%) in group I and 15(75.0%) in group II patients came from upper (20,000->50,000 tk) income group family. Single family was found 16(80.0%) in group I and 13(65.0%) in group II.

(Table 9) shows bottle feeding status was found 4(20.0%) in group I and 6(30.0%) in group II. Seven 7(35.0%) in group I and 5(25.0%) in group II respondents mentioned that does her child actively/voluntarily take food to mouth by himself. Six (30.0%) in group I and 7(35.0%) in group II respondents mentioned that they passively feed her child while he is unmindful during watching the television or playing his favorite game. Nineteen (95.0%) in group I and 17(85.0%) respondents mentioned that he have an excessive affinity for junk foods such as, chocolates, chips, chanachur. aachar (prickles) etc. Eighteen (90.0%) in group I and 15(75.0%) in group II respondents mentioned that child distress trying new foods. Five (25.0%) in group I and 9(45.0%) in group II respondents mentioned that obsession with familiarity, such as one particular make and flavor. Increase ammonia pre was 14(70.0%) in group I and 12(60.0%) in group II. Increase lactate pre was found 13(65.0%) in group I and 11(55.0%) in group II. The difference was not statistically significant (p>0.005) between two groups.

s=significant; ns=not significant.

P value reached from unpaired t-test.

(Table 10) shows specific behaviors of the study patients, it was observed that mean pre social relationship was found 2.86±0.37 in group I and 2.76 in group I. Mean post social relationship was 3.67±0.47 in group I and 3.87±0.51 in group II. Mean pre per interaction was found 2.43±0.53 in group I and 2.28±0.48 in group II. Mean post peer interaction was 3.25±0.60 in group I and 3.29±0.53 in group II. Mean pre communication was found 2.58±0.61 in group I and 2.12±0.77 in group II. Mean post communication was found 3.77+0.61 in group I and 3.65±0.68 in group II. Mean pre sensory responses were found 2.82±0.59 in group I and 2.96±0.75 in group II. Mean post sensory responses was found 3.58±0.55 in group I and 3.64±0.48 in group II. Only mean pre communication difference was statistically significant (p<0.05) but olhevs were not statistically significant (p>0.05) between two groups. All specific behaviors between pre aaa'-ecB was statistically significant (pO.OS) within the groups.

Discussion

A total of 40 children (6 years or under 6 years) having Autism Spectrum Disorders (ASD), that of randomly selected (lottery method) 20 children received a specific dietary intervention was considered as group I and 20 children who not received a specific dietary intervention was considered as group II, who came in the MTW (More than word) clinic were included in this study. Children having autism with associated illness such as epilepsy and other neuro developmental disorder and children who did not meet the ICD-10 criteria for autism were excluded from the study. The present study findings were discussed and compared with previously published relevant studies. In this current study it was observed that Autism Spectrum Disorders was more common in male children, which was 85.0% and 95.0% in group I and group II respectively. Male to female ratio was 5.7:1 in group I and 19:1 in group II and 9:1 in the whole study patients. The difference was not statistically significant (p>0.05) between two groups. Millward et al.¹⁸ determined the efficacy of gluten and/or casein free diets as an intervention to improve behavior, cognitive and social functioning in individuals with autism. Two small randomized controlled trials (RCTs) were identified (n = 35). No meta-analysis was possible. There were only three significant treatment effects in favor of the intervention: overall autistic traits, mean difference (MD) = -5.60 (95% Cl -9.02 to -2.18), z = 3.21, p=0.001¹²; social isolation, MD = -3.20 (95% Cl -5.20 to 1.20). z = 3.14, p = 0.002) and overall ability to communicate and interact, MD = 1.70 (95% Cl 0.50 to 2.90), z = 2.77, p = 0.006)¹⁹. In addition three outcomes showed no significant difference between the treatment and control group and they were unable to calculate mean differences for ten outcomes because the data were skewed. Current evidence for efficacy of these diets is poor. Experts disagree about the causes and significance of the recent increases in the prevalence of autism spectrum disorders (ASDs) reported by Kim et al.²⁰. Limited data on population base rates contribute to this uncertainty. Using a population-based sample, the authors sought to estimate the prevalence and describe the clinical characteristics of ASDs in school-age children. The target population was all 7- to 12-year-old children in a South Korean community; the study used a high- probability group from special education schools and a disability registry and a low-probability, general-population sample from regular schools. To identify cases, the authors used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of children who screened positive were offered comprehensive assessments using standardized diagnostic procedures. The prevalence of ASDs was estimated to be 2.64% (95% 01=1.91-3.37), with 1.89% (95% 01=1.43-2.36) in the general-population sample and 0.75% (95% 01=0.58-0.93) in the high-probability group. ASD characteristics differed between the two groups: the male-to-female ratios were 2.5:1 and 5.1:1 in the general population sample and high-probability group, respectively, and the ratios of autistic disorders to other ASD subtypes were 1:2.6 and 2.6:1, respectively; 12% in the general-population sample had superior IQs, compared with 7% in the high-probability group; and 16% in the general-population sample had intellectual disability, compared with 59% in the high-probability group. Two-thirds of ASD cases in the overall sample were in the mainstream school population, undiagnosed and untreated. There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). Whitely et al.²¹ reported results from a two-stage, 24-month, randomized, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomization. Kim et al.²⁰ mentioned in their study that the male-to-female ratios were 2.5:1 and 5.1:1 in the general population sample and high-probability group, respectively. Parker²⁴ found the sex ratio in the total sample was five boys to one female, similar to the average 4:1 given in the literature observed by Poustka et al.²⁵. Similarly, Rahman et al.⁶ showed male to female ratio was 1.7:1 having autism spectrum disorders (ASD). Baron-Cohen et al.²⁶ noted that predominance of ASD and other neuro-develop mental disorders in boys may be an "extreme expression of the male brain". This concept states that boys and girls brains begin to differ early in the uterus. These differences result in different strengths and weaknesses. ASC may be an example of the male brain development gone too far. In this present study it was observed that majority patients were came from Dhaka district in both groups (80.0% in group I and 90.0% in group II). The difference was not statistically significant (p>0.05) between two groups. Rahman et al.⁶ mentioned that the children diagnosed with autism had parents from 96.0% urban and 4.0% from rural area. In this current series it was observed that most (70.0% group I vs. 65.0% group II) of the children had no schooling in both groups. Formal schooling was found only 20.0% and 25.0% in group I and group II respectively. The difference was not statistically significant (p>0.05) between two groups. Kim et al.²⁰ found in their study that birth cohort distributions for children in the disability registry/special education schools and regular-schools groups were similar, with significantly more boys in the disability registry/special education schools 82.0% compared with 48.0% (p<0.001). In this present series it was observed that majority of the mother underwent caesarean section in both groups, which was 80.0% in group I and 75.0% in group II. The difference was not statistically significant (p>0.05) between two groups. On the other hand, it was observed that majority patient's had birth history uneventful in both groups, which was 90.0% in group I and 85.0% in group II. Eventful birth history was found 10.0% and 15.0% in group I and group II respectively. The difference was not statistically significant (p>0.05) between two groups. In this series it was observed that most of the fathers were master degree pass in both groups that was 65.0% in group I and 85.0% in group II. More than a half (55.0%) of the fathers was service holder in group I and 25.0% in group II. Most (70.0%) of the mothers were master’s degree pass in group I and 75.0% in group II. Majority mothers had professional occupations. Eighty percent in group I and 75.0% in group II patients came from upper (20,000->50,000 tk) income family group. Single family was found 80.0% in group I and 65.0% in group II. Similarly, Rahman et al.⁶ showed both of the parents (97.0% father and 79.0% mother) were highly educated. Most (62.0%) of the fathers were service holder, businessman 28.0% and doctor 11.0%. Majority (62.0%) of the patients came from upper income class, 33.0% middle class and 4.0% came from poor family. Typical symptoms of ASD, including repetitive mannerisms, impulsive acts, emotional outbursts, restricted interests, inflexible adherence to specific routines, and social communication deficits, were found to be correlated with executive dysfunctions in response selection, alteration, and inhibition²². Their results are encouraging since commonly used behavioral interventions for ASD children are very time consuming and not cost-effective, while the present diet modification is less time consuming and more economical. In this current study it was observed that bottle feeding was found 20.0% in group I and 30.0% in group II. More than one third (35.0%) in group I and 25.0% in group II respondents mentioned that her child actively/voluntarily take food to mouth by himself. Thirty percent (30.0%) in group I and 35.0% in group II respondents mentioned that they passively feed her child while he is unmindful during watching the television or playing his favorite game. Ninety five percent (95.0%) in group I and 85.0% in group II respondents mentioned that he have an excessive affinity for junk foods such as, chocolates, chips, chanachur, aachar (prickles) etc. Ninety percent (90.0%) in group I and 75.0% in group II respondents mentioned that child distress trying new foods. One fourth (25.0%) in group I and 45.0% in group II respondents mentioned that obsession with familiarity, such as one particular make and flavor. Increase ammonia pre was found 70.0% in group I and 60.0% in group II. Increase lactate pre was observed 65.0% in group I and 55.0% in group II. The above findings about dietary question were almost similar between two groups regarding the. Many dietitians still remain uncertain on the effectiveness of the GF/CF diet in children with ASD²⁴. With a growing number of referrals to the dietetic service regarding this area obtained by Bowers²⁷, more research is needed mentioned by Parker²⁴ to provide practicing dietitians with up to date information. Forty dietitians responded to the straw poll with the majority of practicing dietitians (62.5%) believing the GF/CF diet had a role in the management of ASD, however 17.5% did not answer this question indicating the uncertainty in this area reported by Parker²⁴. The idea of food as medicine has also drawn increasing attention in western scientific research. A number of studies done by Craig²⁸; Fraser²⁹; Beezhold, Johnston, and Daigle³⁰ have supported the beneficial effects of a vegetarian or vegan diet in promoting the health of cardiovascular and digestive systems, reducing cancers and degenerative diseases and improving mood. Isaacs et al.³¹ and Gale et al.³² studies have also revealed a significant linkage between a balanced nutritional diet and level of cognitive functions and cognitive development in early life. However, many of them are observational studies and there is also counterevidence against the positive dietary effects obtained by Benton³³. Therefore, it remains inconclusive in terms of the actual outcomes and the choice of type of diet. In this current study about the specific behaviors, it was observed that mean pre social relationship was found 2.86±0.37 in group I and 2.76 in group I. The mean post social relationship was 3.67±0.47 in group I and 3.87±0.51 in group II, which was significantly (P<0.05) improved. Mean pre per interaction was found 2.43+0.53 in group I and 2.28±0.48 in group II. The mean post peer interaction was 3.25±0.60 in group I and 3.29±0.53 in group II, that was also significantly (P<0.05) improved. Mean pre communication was found 2.58±0.61 in group I and 2.12±0.77 in group II. Mean post communication was found 3.77±0.61 in group I and 3.65±0.68 in group II, which was significantly (P<0.05) improved. Mean pre sensory a response was found 2.82+0.59 in group I and 2.96±0.75 in group II. The mean post sensory responses was found 3.58±0.55 in group I and 3.64±0.48 in group II which was significantly (PO.05) improved. All specific behaviors were significantly (p<0.05) improved within the groups from pre to post intervention period, but no significant (p>0.05) difference were found between the groups during post intervention period. Chan et al.²² finding may suggest an alternative or complementary intervention for the executive control of behaviors among ASD children. It should be noted that the positive effect of diet modification was also applicable to the low-functioning children with IQ at or below 70 in their experiment. Specifically, there were 8 low-functioning children in the experimental group and 9 in the control group. The control group did not show such improvement in Chan et al.²² study. However, its long term effect is still unknown which is worth further investigation. In addition, the sample size of the low-functioning subgroup is relatively small in their study; therefore, future studies with larger sample sizes will be helpful to verify the effect of diet modification obtained by the authors. Given the preliminary evidence on the effects of diet change in the low-functioning subgroups, it will also be worth investigating if this can benefit patients with severe brain disorders or physical disabilities (e.g., demented or stroke patients) in a well-controlled study.

Conclusion

The improvements in behavior of children with ASD were almost similar between two groups. This randomized control trial (RCT) was carried out with an aim to find out any difference in behavior of Autism Spectrum Disorders (ASD) children before and after a dietary intervention and to find out the difference in behavior of study children between specific dietary intervention received and children not received this specific intervention as well as to find out the improvement in behavior of children having ASD between the two groups. This concept states that boys and girls brains begin to differ early in the uterus.

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