Perceptions of Parents on Management of Food Allergy in Children with Autism Spectrum Disorder (ASD) in Saudi Arabia

Background: Food allergy is one of the most serious health concerns spread across the globe. Its awareness and management are undervalued, especially in children with autism spectrum disorders (ASD). The aim of this study is to explore the perception of parents of autistic children from Saudi Arabia on the prevalence, knowledge, awareness and management of food allergens. Methods: A cross-sectional exploratory self-administrated online survey was conducted in Saudi Arabia, where 125 parents of autistic children voluntarily took part in the survey from April to August 2022. Results: This study indicates that less than one-fourth of autistic children suffering from food allergies, while most of them are allergic to proteins mainly. Examination of the knowledge level of these parents regarding food allergies, depending upon the score of correct answers given by them, showed that a majority of parents had a moderate level of knowledge on food allergy. Even though there was awareness about food allergens, the use of medical interventions was not employed much. However, the parents were mindful of food labeling and found it to be useful in avoiding known food allergies. Mediating effects of food allergy were observed in the relationship between food allergy knowledge and its management. Moreover, the source of information about food allergies was also found to be significantly associated with the knowledge score and the level of awareness regarding food allergies. This study provides evidence that there is a significant influence of food allergy knowledge of parents of autistic children on its management among autistic children from Saudi Arabia, with awareness of food allergies as the mediator. Conclusions: This is the first study where the prevalence, knowledge and management, along with awareness of food allergy, has been empirically explored through the perception of parents of autistic children.


Introduction
Food allergy can be described as the "adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food", which varies from food intolerance as the latter is a "nonimmune reaction that includes metabolic, toxic, pharmacologic, and undefined mechanisms" [1]. The clinical response of food allergy varies from being mildly discomforting (tingling/itching) to severe life-threatening issues and even mortality of the affected individuals [2]. As shown in WHO [3], food allergies are highly common and prevalent in 1 to 3% of adults and 4 to 6% of children across the world. Over the years, the occurrence of food allergies has drastically increased, going beyond 25 to 30% [4] and, in some cases, up to 66% [5]. Even though all food items can be potentially allergenic, in general, seventy or more types of food items have been found to be causing food allergy [3]. behavioral issues observed in autistic children. The exclusion of potential allergens is the primary treatment modality against any food allergy, irrespective of the neurological condition [1] was also found also to be beneficial in managing the behavioral issues of autistic children [13]. In contrast to the above studies, evaluating the risk factors of ASD and Attention Deficit Hyperactivity Disorder (ADHD) in a retrospective study of 134 children from Jeddah, Saudi Arabia, food as a risk factor was found to be unassociated with ASD and ADHD [11]. Similarly, in an observational study with 30 autistic boys and three autistic girls, these children did not demonstrate any level of gluten sensitivity [23]. This implies the presence of conflicting results and, thus, warrants more clarity in this regard.
None of the studies elaborate on the perception of parents with autistic children in terms of their knowledge and awareness of the concept of food allergy, even when the autistic abdominal symptom seems to be associated with food allergies [4,12,24]. Most of the studies, even on the perception of food allergy among parents, involved only frequency and percentage analysis; there were hardly any inferential studies on this topic. The present study intends to investigate the perception of parents of autistic children living in Saudi Arabia in terms of prevalence, knowledge and awareness of food allergy. Along with this, the mediating effect of awareness on the relationship between knowledge of food allergies of parents and its management for better well-being among these children was also examined. Based on the aim of the study, the following three objectives were outlined, keeping in mind the Saudi Arabian population for our study:

1.
To explore the level of prevalence of food allergy, the main types of allergens and symptoms among autistic children.

2.
To estimate the level of knowledge of parents about food allergies in children with autism. 3.
To understand the impact of parental knowledge of food allergy on its management to ensure healthy well-being of autistic children and mediated by awareness towards food allergy.

Study Design
For this study, a nationwide observational cross-sectional survey in Saudi Arabia through web-based questionnaire was formulated by the researcher. A positivistic exploratory research design employing a deductive research approach to understand the extent of food allergy management among autistic children was undertaken. The duration of the study was from April 2022 to August 2022.

Study Population
The sample population intended for this study comprised 125 parents of children with autism selected using the convenient non-probability sampling technique. The inclusion criteria included consent from the parents, age group of children in the range of 2 to 18 years, and diagnosis of autism or ASD. The exclusion criteria were as follows: (a) autism related to any genetic syndrome; epilepsy; celiac problems, (b) being a single child, (c) any known food allergy, such as lactose intolerance, nut allergy, etc., or (d) children on a special diet. This research was performed in conformity with the rules of the 1975 Helsinki Declaration. Approval was attained from the ethical committee of the College of Applied Medical Sciences in Taibah University, Medina, Saudi Arabia (2022/141/207/CLN) on 10 April 2022.

Measures
A well-structured online questionnaire was prepared by the researchers based on the literature reviews of past studies in this area. This method was found to be appropriate because of its greater geographic distance coverage, reduced cost of traveling, and the easy maintenance of proper COVID-19 protocols during data collection [25,26]. The questionnaire consisted of five main parts: demographic information of parents and their autistic children. Within the socio-demographics of parents, their age, gender, nationality, marital status, occupation, educational level, number of family members, region of residence and any history of food allergy in the family was gathered, while for the child, information was noted about their gender, age and presence of any sibling with autism. The prevalence of food allergy among autistic children was measured by enquiring about the existence of allergic reactions in the child or their siblings diagnosed either by the parents or by the doctors, followed by the age at which the child got his first allergic reaction. Along with this, any known ways by which the child obtained the allergy, the duration of the allergy till its signs wear off, types of food allergens and the common symptoms of allergy due to food were also points of inquiry. The next set of 16 statements evaluated the level of knowledge or perception of parents on food allergies with response options of yes, no and not sure.
A scoring system based on the right answers was employed to calculate the knowledge score. Each right answer was given a score of one. Those parents who had a score of less than or equal to 8 were considered as having poor knowledge, while individuals answering 9 to 11 statements correctly were considered to have moderate knowledge and participants who identified 12 or more correct statements fell under the category of parents with good knowledge on food allergy. Awareness of food allergy and Management of food allergy with respect to medical interventions and understanding of food labeling was measured using 5-point Likert scale, ranging from 1 = Not at all to 5 = Always. In addition to this, the most common source of information about food allergies for the parents of autistic children was also probed. The final questionnaire was also translated into Arabic for a better understanding of the participants and sent to them through their emails. Under ethical considerations, it should be observed that the consent forms were distributed by the researcher before the administration of the questionnaires. Only after receiving acceptance of consent mail was the questionnaire sent to the voluntary participants. Moreover, the participants were assured that the data would be used only for academic purposes, be kept confidential and be inaccessible to any third party other than the researcher.

Data Analysis
Statistical software (SPSS version 24) was employed to convert the collected raw data into numerical data which was subjected to statistical analyses. This statistical tool has been successfully used for obtaining meaningful inferences [27]. All the study variables were measured using frequency and percentage and chi-squared test was applied to examine the association between the study variables. The influence of knowledge of food allergy on management of food allergy was examined through linear regression analysis. Along with this, mediation analysis was conducted between knowledge of parents on food allergy of autistic children and management of food allergy, mediated through awareness. The associations were accepted to be statistically significant when the p-value was observed to be less than 0.05 at 95% confidence level. Table 1 elucidates the sociodemographic characteristics of the participating parents and their children diagnosed with ASD. Out of the total of 125 responding parents, the majority of them were 31-to 40-year-old married graduate females with Saudi nationality and working in private sector, having a family of three members with a medium-range family income living in the eastern region of Saudi Arabia. Most of them (83.2%) had a family history of food allergy. Out of the 125 autistic children, 52.8% of them were boys and the rest, 47.2% of them, were girls. More than 58% of them were within the age group of two to four years old, and the majority (82.4%) of them did not have a sibling with autism.  Table 2 presents the frequency of autistic children and others with food allergies. It was observed that only 29 (23.4%) of the children with ASD suffered from a food allergy, while only 36% of the parents agreed that their other children also had some type of food allergy. Regarding the age at which food allergy was first observed in the autistic children, it was found that food allergy occurred when they were mostly one to two years old (45.1%), followed by 20.9% of them, whose first symptom was detected when they were more than six years old, while 19.8% of them claimed that their children were only three to six years old when they got their first allergic attack. Moreover, only 14.3% of them got their first allergic reaction before their first birthday. The primary mechanism of getting the food allergy was through eating (65.5%), followed by smelling (10.3%) or by touching (6.9%). About 17.2% of autistic children got their allergy from a combination of eating, smelling as well as touching. When enquired about the duration till the signs of allergy wear off, the majority (69%) of the parents construed that the allergic reactions typically last for some minutes to hours, whereas the rest (31%) of them took days to wear off the allergy.  Table 3 gives the distribution of children with respect to the various categories of food allergens. It was observed that allergy due to consumption of food rich in proteins (18.4%) was most common among autistic children, followed by cereals (15.2%), cocoa (9.6%), fruits and nuts (8.8%) and vegetables (5.6%). Within proteins, cow milk was found to be the most frequent allergen, impacting 72.4% of the affected children, followed by seafood (69%), fish (37.9%) and chicken (20.7%). Among vegetables, beans caused allergy in 24.1% of the allergic children, followed by eggplant and tomato (17.2% each). Potato, spinach and onion were non-allergens for this set of children. Banana was the reason for allergy in 20.7% of the children, followed by strawberry (13.8%), grapes (10.3%) and apples (3.4%). Between the dry fruits, almonds, peanuts and hazelnuts equally contributed to 24.1% of the affected children and wheat and rice impacted 65.5% and 31.0% of these children, respectively. Cocoa too caused allergy in 41.4% of the 29 children who had a food allergy. No statistically significant association was observed between the demographics of the autistic children with the type of allergens (p > 0.5).

Prevalence of Food Allergy among Autistic Children
The top three most common symptom of food allergy observed in autistic children was skin redness (72.4%), followed by skin rash (69.0%) and itching (62.1%). The other symptoms include shortness of breath (31.0%); swelling of body parts, especially the tongue (20.7%); abdominal pain (17.2%); nausea and vomiting (13.8% each); difficulty in swallowing and diarrhea (10.3% each) and runny nose and cough (6.9% each).

Knowledge Level of Parents about Food Allergies in Children with Autism
The knowledge of parents of autistic children on food allergies was assessed by asking them true or false about 16 related statements (Table 4). Based on the knowledge scoring system as explained in the methodology, it was estimated that more than 62.2% of correct answers were given by the parents and the majority (63.2%) of them had a moderate level of knowledge about food allergens (score of 9 to 11 out of 16), while 23.3% had good knowledge (score of 12 to 16) and only 13.6% had poor knowledge (score of 1 to 8) on these allergies ( Figure 1).  Furthermore, the association of the knowledge score of parents with their demographics was analyzed (Table 5), and it was found to be statistically significant in terms of their age (chi-square = 34.011, p < 0.01), nationality (chi-square = 26.343, p < 0.01), educational qualification (chi-square = 17.126, p < 0.01), and family history of food allergy (chisquare = 51.749, p < 0.001). Poor knowledge was associated with young parents (18 to 30 years) and non-Saudi nationals with no family history of food allergy, which may be due to inexperience. Gender of the parent, their occupation and location of residence did not play any role in the knowledge of food allergy among these parents with autistic children.  Furthermore, the association of the knowledge score of parents with their demographics was analyzed (Table 5), and it was found to be statistically significant in terms of their age (chi-square = 34.011, p < 0.01), nationality (chi-square = 26.343, p < 0.01), educational qualification (chi-square = 17.126, p < 0.01), and family history of food allergy (chi-square = 51.749, p < 0.001). Poor knowledge was associated with young parents (18 to 30 years) and non-Saudi nationals with no family history of food allergy, which may be due to inexperience. Gender of the parent, their occupation and location of residence did not play any role in the knowledge of food allergy among these parents with autistic children.

Awareness and Management of Food Allergies
With respect to food allergy awareness, the majority of parents (41.6%) felt that they were 'somewhat' aware of the food items that cause food allergy in their child and often felt that the food should be monitored before their child eats it (36%). The management of food allergies was evaluated through two sub-variables, such as the use of medical interventions and the understanding of food labeling. Within medical interventions, the majority of parents often kept an epinephrine pen handy (34.4%). More than 38% of them had to send their child to the emergency room (ER) or have been admitted to the hospital due to food allergies. Moreover, the parents very well knew which doctor to be consulted when their child got an allergic reaction. In terms of food labeling, more than half (52.8%) of the participants believed that food labeling is extremely helpful in avoiding known medical allergies. Almost half of them were aware of the information for labeling food allergens, while 46.4% of them were cautious about the contents in the food that was given to the child. Figure 2 summarizes the role of food allergy awareness as a mediator on the impact of knowledge on the management of food allergies. Table 6 presents the results of the mediation analysis to evaluate the total effect (C), the indirect effect (ab) and the direct effect (C') and their associated 95% confidence intervals. According to Figure 2, the outcome variable for the analysis was the management of food allergy. The predictor variable for the analysis was knowledge of food allergies, while awareness of food allergy was evaluated as the mediator. The results show that the level of knowledge positively predicts the management of food allergy (β = 0.24 for moderate and β = 0.33 for high knowledge score of parents, p < 0.05) (Model 1). Analysing the indirect effects, results reveal that awareness completely mediates the relationship between knowledge and management of food allergy in parents with moderate knowledge of food allergy, but awareness of food allergy partially mediates the same relationship in parents with a high level of allergy knowledge.

Awareness and Management of Food Allergies
With respect to food allergy awareness, the majority of parents (41.6%) felt that they were 'somewhat' aware of the food items that cause food allergy in their child and often felt that the food should be monitored before their child eats it (36%). The management of food allergies was evaluated through two sub-variables, such as the use of medical interventions and the understanding of food labeling. Within medical interventions, the majority of parents often kept an epinephrine pen handy (34.4%). More than 38% of them had to send their child to the emergency room (ER) or have been admitted to the hospital due to food allergies. Moreover, the parents very well knew which doctor to be consulted when their child got an allergic reaction. In terms of food labeling, more than half (52.8%) of the participants believed that food labeling is extremely helpful in avoiding known medical allergies. Almost half of them were aware of the information for labeling food allergens, while 46.4% of them were cautious about the contents in the food that was given to the child. Figure 2 summarizes the role of food allergy awareness as a mediator on the impact of knowledge on the management of food allergies. Table 6 presents the results of the mediation analysis to evaluate the total effect (C), the indirect effect (ab) and the direct effect (C') and their associated 95% confidence intervals. According to Figure 2, the outcome variable for the analysis was the management of food allergy. The predictor variable for the analysis was knowledge of food allergies, while awareness of food allergy was evaluated as the mediator. The results show that the level of knowledge positively predicts the management of food allergy (β = 0.24 for moderate and β = 0.33 for high knowledge score of parents, p < 0.05) (Model 1). Analysing the indirect effects, results reveal that awareness completely mediates the relationship between knowledge and management of food allergy in parents with moderate knowledge of food allergy, but awareness of food allergy partially mediates the same relationship in parents with a high level of allergy knowledge.  Table 6. Effect of mediation by awareness on relationship between knowledge and management of food allergy.

Source of Information about Food Allergies
In Table 7, the majority (42.4%) of the parents were dependent upon social media as the main source of information on food allergy, followed by their learnings from their education (14.4%) and the advice given by doctors (12.8%). Social media has been argued to play a critical part in enhancing the awareness of parents, thereby altering their attitude towards food allergy [17]. Significant associations were observed between the source of information with the knowledge level on food allergy (chi-square = 20.376, p < 0.01) and awareness of food allergy (chi-square = 19.374, p < 0.01). It was observed that the advice of the doctor or the health care professional e.g. dietitians was considered a better source of quality information and the best source for food allergy compared to social media. Table 7. Association of source of information about food allergy with knowledge score and awareness of food allergy.

Discussion
The findings of this study deal with knowledge and awareness of food allergy and its management among parents of autistic children in Saudi Arabia. Among the studied parental attributes, it was observed that the majority of the participating parents of the autistic children were in their middle age and non-graduates, as also observed by Alqahtani et al., [17], where the focus was on the perception of food allergy among mothers whose children suffered from food allergy. Similar to Alanazi et al., [16], both mothers and fathers equally contributed to the data collection for this study. In a separate study from Saudi Arabia, the participating parents (mothers) were housewives and much older in age than our study population [18].
The selected participants reported that less than one-fourth of the autistic children faced the issue of food allergy. Regarding the prevalence of food allergies in autistic children, the findings of the present study show a much higher degree of prevalence compared to the levels reported by others [12,13], where the prevalence was up to 14% and 11%, respectively, in children with autism. In another study, only 12% and 17.5% of the children from cities in Saudi Arabia were allergic to food [16,18]. Similar results were observed by Alqahtani et al., [17], where the prevalence was about 29%. Moreover, Alotaibi et al., [15] reported food allergies to be present in almost 50% of children living in Saudi Arabia. In adults, the prevalence of food allergy was restricted to 21.4% [2]. This difference may be due to the fact that food allergy varies with changes in geographical location and also has been expected to be more evident in autistic children [4]. Moreover, the observed higher frequency of food allergies was common in the first couple of years of life, as observed in our study was also reported by [17,28]. However, Alotaibi et al., [15] observed that the majority of the children were less than one year old when they had their first episode of food allergy. It should be kept in mind that increased prevalence towards food allergy among austistic children found in this study may be due to the self-reporting by the parents or the caregiver. There is a possibility of an intrisic bias, therefore, this requires further validation performed in a scientific manner. Our findings on mechanism of food allergy and duration till signs of allergy wears off were found to be similar as also observed by Alqahtani et al., [17], where eating was the primary mode of getting the allergy and the allergy stayed for minutes to hours in the children. However, Alotaibi et al., [15] found that sometimes the timing of the allergic response to develop symptoms itself can stretch beyond 24 h in rare cases. Most of them in our case had allergic symptoms within 1 to 2 h of exposure to the allergen.
Among all food categories, the primary allergen for autistic children, as observed by their parents' involved food rich in proteins. This can be supported by Youssef et al., [24], wherein it was reported that digesting protein is difficult for children with autism. Within proteins, milk was observed to be the primary source of allergy in the children whose parents participated in our study. This is contradictory to Alotaibi et al., [15] and Alanazi et al. [16], where fish caused food allergy in the majority of children from Saudi Arabia, followed by beans. Shellfish, followed by egg and milk, were found to be the most common allergens in children from Saudi Arabia, as observed by Alqahtani et al., [17]. However, it was also reported that egg-induced maximum food allergy in adults [2] as well as children [28] from Saudi Arabia. Moreover, WHO [3] reports on food allergies suggested that egg along with milk allergies are more common in infants compared to adults. In a separate study, peanut, coffee, crab, apple and potato were found to be highly allergenic in autistic children from India, while peanut was the primary allergen for Canadian children [14], which was completely contradictory to our observations of any form of nuts. As reported in Gomaa et al., [18], nuts are the most common type of food causing allergies in children from Saudi Arabia.
Among the most common symptoms, redness was also observed in the majority of children as an allergic reaction by [18,28] in children from UAE and Saudi Arabia, respectively. Contradictory results were observed in terms of the most frequent symptom observed due to food allergy by [15,16], where parents of children living in the cities of Saudi Arabia reported itching to be the most frequent symptom.
Compared to the findings of the present study, where the majority of them had moderate levels of knowledge on food allergy, the majority of mothers from a study in Saudi Arabia were found to have poor allergy knowledge [18]. The knowledge of food allergy in parents has been observed to vary drastically depending upon the food item in question, as also observed by [16]. Regarding the association studies between demographics and knowledge of food allergy, age was found to be associated with knowledge scores in a study with mothers of allergic children from Saudi Arabia [18], similar to our findings. However, in contrast to our study, the educational qualification and occupation, in this case, were unrelated to knowledge levels.
Contrary to our findings on the level of food allergy awareness, [15,17] reported conflicting observations in this regard among the Saudi population. Gomaa et al., [18] suggested that the knowledge and awareness were both poor in Saudi Arabian mothers. Apart from this, even the awareness of pediatricians in Kuwait on food allergy was also observed to be limited [29]. As reported in Alotaibi et al., [15], the majority of the parents did not seek much medical advice regarding food allergy even after the symptoms were observed. The use of epinephrine is not quite common among the Saudi Arabia population as the awareness about it seems to be low [19,30]. People, even school authorities or teachers, hardly know about this medication. Even though the majority of the parents in our study were aware of the food allergen in their child, the management levels towards controlling or avoiding allergies were found to be poor. This was also implied by [31], where food allergen knowledge was negatively but insignificantly related to food allergy management practices.
A significant influence of knowledge of food allergy of parents on the management of food allergy was observed, which was mediated by awareness of food allergy. The mediation analysis showed that parents with good knowledge of food allergy significantly influence food allergy management in autistic children. However, parents with a moderate level of knowledge have hardly any impact on allergy management. Therefore, awareness in this aspect is essential, especially for the population who have a moderate level of knowledge of food allergies. As expected, the management can be better controlled by enhancing knowledge and awareness of it. Therefore, raising awareness of food allergy is required for Saudi society, especially with regard to autistic children, as also realized by [19]. In fact, not only autistic children; WHO [3] has pointed out that awareness in this aspect is the "1st step in protecting individuals with food allergies" among all. Moreover, the criticality of this issue and the need for enhancing awareness of food allergies among the general population has also been reported from studies of other countries [7,9,31,32], as the data on this topic is "scarce" [2]. Unfortunately, none of the studies have done similar mediation analyses in this aspect; therefore, our findings could not be compared much with others.
Supporting our results from this study, social media has been argued to play a critical part in enhancing the awareness of parents, thereby altering their attitude towards food allergy [17]. Regarding the source of information, our results matched with the perception of parents of children from Saudi Arabia suffering from food allergies, as also described by [16], where the internet was responsible for the spread of knowledge on possible allergens, followed by books or magazines. However, this study did not evaluate the knowledge level involving food allergy. Our results, however, are in contrast with Soon [31], where the participants from the UK did not apply social media to enhance their knowledge of food allergens.
Even though this has been one of the pioneering contributions to the outlook involving food allergies in autistic children, this study was restricted in terms of sample size, the scope of bias and misreporting as this study was based on self-reporting rather than through clinical guidelines. Moreover, no immunological tests were conducted to actually assess the immune response of the affected children. In addition, no neurotypical children were considered for the study. Moreover, the degree of autism was also not studied during the course of the study. Therefore, increasing the sample size, obtaining validation from doctors about the genuine nature of food allergy, and comparing it with non-autistic children from the same area can lead to an in-depth analysis of the issue, which will be helpful in obtaining the whole picture as a part of future research. Furthermore, research should also focus on finding easier methods for identifying food allergies and understanding the various aspects of food allergy management, which will be beneficial in managing ASD as well.

Conclusions and Future Scope
The present study explored the prevalence, awareness and management of food allergies through the perceptions of parents with autistic children and showed that food allergy can be a major problem among autistic children, even though this is yet to be supported by scientific evidence. A high prevalence of food allergies was observed in these children, thereby implying that it is crucial to spread awareness of food allergens among the population in order to have better management of reactions to food allergies. Moreover, this study also elaborates on the types of food allergens and the symptoms observed during allergies in autistic children. Since the overall knowledge among the majority of parents was found to be moderate, an increase in knowledge is urgently warranted, especially among parents of children with developmental disorders. Moreover, awareness was found to completely mediate the relationship of knowledge on food allergy management in terms of parents with a moderate level of knowledge, while for parents with a high level of food allergy knowledge, awareness only partially mediated the relationship. From our study, it can be suggested that awareness of food allergy should take precedence by the healthcare ministry. Moreover, the healthcare agencies, as well as the healthcare ministries, should start intensive programs that ensure an increase in correct and accurate knowledge about food allergies. Our results emphasize that food allergy management is not being considered seriously among this kind of population, which is a matter of concern not only for the patients but also for their caregivers, the government, doctors, hospitals and society as a whole. This task is essential for ensuring the healthy well-being of autistic children since these children are more affiliated to be impacted by food allergies compared to children who do not have ASD. However, this study in no way implies that food allergy is the causal agent of ASD among children and, therefore, needs to be confirmed through medical analysis. To the best of our knowledge, this is the first study exploring the awareness and management aspects regarding food allergy in children with autism as well the role of awareness as a mediator, where knowledge influences food management. Another key strength of this study includes the inclusion of participants from all regions of Saudi Arabia.