1 Prevalence and Correlates of Use of Complementary and Alternative Medicine in Children 1 with Autism Spectrum Disorder in Europe 2 3 Erica Salomone 1* , Tony Charman 2 , Helen McConachie 3 , Petra Warreyn 4 , and Working Group 4 4, COST Action ‘Enhancing the Scientific Study of Early Autism’ 5 5 6 1 King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of 7 Psychology, United Kingdom; erica.salomone@kcl.ac.uk 8 2 King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of 9 Psychology, United Kingdom; tony.charman@kcl.ac.uk 10 3 Institute of Health and Society, Newcastle University, United Kingdom; 11 helen.mcconachie@newcastle.ac.uk 12 4 Department of Experimental Clinical and Health Psychology, Ghent University, Belgium; 13 petra.warreyn@ugent.be 14 5 The Working Group 4 also includes: Anett Kaale, anett.kaale@r-bup.no (Norway); Bernadette 15 Rogé, roge@univ-tlse2.fr and Frederique Bonnet-Brilhaut, frederique.brilhault@univ-tours.fr 16 (France), Iris Oosterling, i.oosterling@karakter.com (the Netherlands), Selda Ozdemir, 17 seldaozdemir@gazi.edu.tr (Turkey), Antonio Narzisi, antonio.narzisi@inpe.unipi.it and Filippo 18 Muratori f.muratori@inpe.unipi.it, (Italy), Joaquin Fuentes, fuentes.j@telefonica.net (Spain), Mikael 19 Heimann mikael.heimann@liu.se, (Sweden), Michele Noterdaeme, 20 noterdaeme.michele@josefinum.de, Christine Freitag, ChristineMargarete.Freitag@kgu.de, Luise 21 Poustka, Luise.Poustka@zi-mannheim.de and Judith Sinzig, judith.sinzig@lvr.de(Germany), Sue 22 Fletcher-Watson, sfwatson@staffmail.ed.ac.uk and Jonathan Green, 23 jonathan.green@manchester.ac.uk (the UK). 24 mailto:erica.salomone@kcl.ac.uk mailto:tony.charman@kcl.ac.uk mailto:helen.mcconachie@newcastle.ac.uk mailto:petra.warreyn@ugent.be mailto:anett.kaale@r-bup.no mailto:roge@univ-tlse2.fr mailto:frederique.brilhault@univ-tours.fr mailto:i.oosterling@karakter.com mailto:seldaozdemir@gazi.edu.tr mailto:antonio.narzisi@inpe.unipi.it mailto:f.muratori@inpe.unipi.it mailto:fuentes.j@telefonica.net mailto:mikael.heimann@liu.se mailto:noterdaeme.michele@josefinum.de mailto:ChristineMargarete.Freitag@kgu.de mailto:Luise.Poustka@zi-mannheim.de mailto:judith.sinzig@lvr.de mailto:sfwatson@staffmail.ed.ac.uk mailto:jonathan.green@manchester.ac.uk 2 * Correspondence should be addressed to: erica.salomone@kcl.ac.uk; +44 (0)207 848 0405 25 26 mailto:erica.salomone@kcl.ac.uk 3 Prevalence and Correlates of Use of Complementary and Alternative Medicine in Children 27 with Autism Spectrum Disorder in Europe 28 29 ABSTRACT 30 This study examined the prevalence and correlates of use of complementary and alternative 31 medicine (CAM) among a sample of children with autism spectrum disorder (ASD) < 7 years 32 in 18 European countries (N=1,680). Forty seven percent of parents reported having tried 33 any CAM approach in the past 6 months. Diets and supplements were used by 25% of the 34 sample and mind-body practices by 24%; other unconventional approaches were used by 35 25% of the families; and a minority of parents reported having tried any invasive or 36 potentially harmful approach (2%). Parents in Eastern Europe reported significantly higher 37 rates of CAM use. In the total sample, children with lower verbal ability and children 38 concurrently using prescribed medications were more likely to be receiving diets or 39 supplements. Concurrent use of high levels of conventional psychosocial intervention was 40 significantly associated with use of mind-body practices. Higher parental educational level 41 also increased the likelihood of both use of diets and supplements and use of mind-body 42 practices. Conclusion: The high prevalence of CAM use among a sample of young children 43 with ASD is an indication that parents need to be supported in the choice of treatments early 44 on in the assessment process, particularly in some parts of Europe. 45 46 47 48 49 4 50 Introduction 51 Autism spectrum disorder (ASD) is a behaviourally defined disorder characterized by 52 impairments in social communication abilities and the presence of restricted and repetitive 53 behaviours and atypical sensory responses [3]. Despite the evidence that behavioural and 54 social communication interventions can ameliorate symptoms and improve outcomes [29] it 55 is not a condition for which a ‘cure’ is currently available. The uncertainty concerning the 56 developmental outcomes, the limitations to existing treatments, and the lack of a simple cure 57 have been indicated as possible reasons for the high prevalence of use of therapies based 58 outside the domain of conventional medical and psychological practice by families of 59 children with autism [21]. Such therapies, generally defined as complementary and 60 alternative medicine (CAM), comprise a myriad of “interventions” that range from unproven 61 and untested treatments to approaches that have been found to be harmful. The National 62 Center for Complementary and Alternative Medicine (NCCAM) distinguishes the following 63 broad areas of CAM: ‘natural products’ (often sold as dietary supplements), ‘mind and body 64 practices’ (such as massage or sensory integration therapy) and a residual category of other 65 complementary health approaches that do not fit neatly in the previous ones, such as 66 homeopathy (http://nccam.nih.gov/). Research on CAM use broadly refers back to this 67 classification, but additional meaningful categories of CAM such as “invasive or potentially 68 unsafe approaches" [1] and other unconventional approaches that are not strictly classifiable 69 as CAM (such as pet therapy) are also often included in such surveys. This, and the fact that 70 the NCCAM classification has changed over time, have led to some inconsistency across 71 studies. 72 http://nccam.nih.gov/ 5 The efficacy of CAM treatment is controversial, but for most of these approaches 73 there simply is not enough evidence to evaluate them [23]. For example, while gluten- and 74 casein-free diets are widely used and reported to be efficacious by parents [40], to date only 75 two RCTs have tested their efficacy, yielding mixed results that prevent any recommendation 76 of these exclusion diets as standard treatments [19,8]. Omega-3 fatty acids are increasingly 77 used in ASD despite lack of understanding on which might be the optimal dosage and 78 insufficient evidence of efficacy [18]. Moreover, while CAM is often used in combination 79 with medication, little is known about potential aversive effects of the interaction between 80 drugs and supplements, which requires careful monitoring [20]. There is some positive 81 evidence for some CAM approaches, such as horse-riding [16] and massage [34]. A 82 Cochrane review of auditory integration training, a costly and theoretically ill-specified 83 treatment, did not find sufficient evidence to support its use [35]. 84 In US based samples, there is some evidence that CAM use in children or young 85 people with ASD is associated with greater functional difficulty [15,32,38], but this has not 86 always been replicated [1]. A higher parental educational level and high levels of use of 87 conventional therapy (>20 hours) have also been found to be associated with CAM use in 88 children with ASD [1]. Cultural and systemic factors (such as families’ own recognition and 89 beliefs around aetiology and course of symptoms as well as the actual availability of 90 conventional therapy) might also play a role in the decision to use CAM [25]. Professionals’ 91 opinions vary widely on the topic [31] and might be another source of influence on family 92 choice. These aspects are likely to differ in different parts of the world [4], however with the 93 exception of a non-systematic review based on professionals’ opinions [41] no studies to date 94 report on the use of CAM in Europe. Moreover, different factors might play a different role in 95 use of specific types of CAM, but this is only beginning to be addressed [32]. The present 96 study aimed at describing the prevalence of use of CAM in Europe, as well as identifying the 97 6 correlates of use of the two main classes of CAM: diets and supplements and mind-body 98 practices. 99 Methods 100 Ethical approval was given by the Research Ethics Committee of the Faculty of 101 Children and Learning, Institute of Education, London, UK. Parents provided informed 102 consent before completing the survey (IOE/ FPS 385). 103 Survey 104 The present study focuses on a set of questions on use of CAM that was part of a 105 wider-scope survey on use of interventions in Europe [33, in press]. The survey was open for 106 completion for 45 days. A total of 1,680 families with a child with ASD aged 7 or younger in 107 18 countries completed the online survey: Belgium, Czech Republic, Denmark, Finland, 108 France, Germany, Hungary, Iceland, Ireland, Italy, Netherlands, Norway, Poland, Portugal, 109 Romania, Spain, The Former Yugoslav Republic of Macedonia and the United Kingdom. 110 Participants were recruited via national parents’ associations who advertised the link on their 111 websites, with the exception of parents in The Former Yugoslav Republic of Macedonia who 112 were recruited through the Paediatric Clinic of Skopje in absence of a national parents’ 113 association and completed a paper version of the survey. Before launching the survey, the 114 questionnaire was piloted with parents from the UK (N=8) and Italy (N=2); as a result of the 115 pilot, the possibility to select a generic intervention if the nature of the approach was not 116 known to the parent was further highlighted in the initial instructions. Participant 117 characteristics are summarised in Table 1. 118 Parent characteristics: General background information on respondents was 119 gathered: relationship to child (mother/father/other) and educational level (below high school 120 7 diploma, high school diploma, bachelor/degree, postgraduate). The educational level was 121 collapsed for analysis into the following two categories: low educational level (up to high 122 school diploma, 37%) and high educational level (degree and postgraduate, 63%). To 123 comply with the relevant legislation on cross-national sharing of sensitive personal data in 124 some of the participating countries, parents were asked to report on the country of residency 125 but data on nationality and ethnicity were not collected. 126 Child characteristics: Information on the age of the child at survey completion was 127 collected and dichotomised to reflect the age at which typically children start school in 128 Europe (below age 5, 52% and 5 years and above, 48%). Child verbal ability was rated by 129 parents selecting one of five options (does not talk; uses single words; uses two- or three-130 word phrases; uses sentences with four or more words; uses complex sentences). The options 131 were collapsed into two categories for the purposes of analysis: low verbal ability (non-verbal 132 or single words speech, 37%) and use of at least phrase speech (63%). 133 Use of conventional therapies and prescription medication: Parents were asked to 134 report on current use of conventional behavioural, developmental and psychosocial 135 intervention (such as applied behavioural analysis, occupational therapy, speech and language 136 therapy…) and medication. A total of 1,529 parents (91%) reported using at least one 137 conventional intervention. The number of conventional interventions used ranged from 1 to 7 138 (M=2.39, SD=1.43; IQR: 1-3); more detailed results are reported in [33, in press]. For the 139 purposes of this analysis, we classified the sample for level of use of conventional treatments. 140 Three levels of use were defined based on the distribution of number of interventions used: 141 no use (0 therapies used; 9%), medium level of use (use of 1-3 therapies; 70.5%) and high 142 level of use (use of 4 or more therapies; 20.5%). Parents reported using at least one 143 medication in 19.7% of cases in the total sample. Use of medication was dichotomised for 144 this analysis into a “use of any medication” binary variable. 145 8 CAM: A list of CAM approaches was drawn from the literature. Parents were asked 146 to endorse all the approaches that they had used with their child in the previous 6 months. 147 The CAM approaches, listed alphabetically in the form, were successively classified into four 148 categories for the purpose of statistical analysis: the three categories proposed by the 149 NCCAM (diets and supplements; mind and body practices; other unconventional approaches) 150 and a fourth category of “invasive, disproven or potentially unsafe CAM” (including 151 chelation, hyperbaric oxygen therapy and packing) which was added [following 1]. 152 153 Data analysis 154 Descriptive statistics were used to report on use of each CAM approach, grouped in 155 four over-arching categories. Prevalence of use of these categories was examined in the total 156 sample and by European regions [37]: Western Europe (Belgium, France, Germany and 157 Netherlands), Northern Europe (Denmark, Finland, Iceland, Ireland, Norway, United 158 Kingdom), Eastern Europe (Czech Republic, Hungary, Poland, Romania) and Southern 159 Europe (Italy, Macedonia, Portugal, Spain). 160 To investigate the association of child and parental characteristics with use of CAM, 161 we conducted logistic regressions on the total sample for two primary outcomes: use of any 162 diets or supplements and use of any body-mind practices. These categories were selected for 163 the analysis on the basis of the following criteria: conceptual relevance, homogeneity of 164 approaches included and frequency of use. In each model, the predictors were: child’s 165 gender, verbal ability and age, parental educational level, use of any prescription medication, 166 use of conventional therapies categorised into three dummy variables (no use of therapy, 167 medium level of use, and high level of use; the first category was used as the reference). 168 9 Results 169 ---- Table 1 about here ----- 170 Frequency of CAM 171 Frequency of use of individual CAM approaches is reported in Table 2. A total of 172 789 respondents (47%) reported using at least one type of CAM. The rate of use of any 173 CAM was significantly higher in Eastern (66%) than in Western (41%, p<.001), Northern 174 (46%, p<.001) and Southern (40%, p<.001) Europe. The prevalence of use in Northern 175 Europe was also significantly higher than in Southern Europe (p=.038). In the total sample, 176 the most commonly used CAM approaches were diets and supplements (24.4% reported 177 using any); use of vitamins was reported by 259 parents (15.4%) and gluten or casein free 178 diets were reported by 227 (13.5%). The proportion of parents reporting using diets and 179 supplements was significantly higher in Eastern Europe (38%) than in Western (17%, 180 p<.001), Northern (28%, p=.003) and Southern Europe (20%, p<.001). Reported use in 181 Northern Europe was also significantly higher than use in Western (p<.001) and Southern 182 Europe (p=.007). Mind and body practices were reported by 395 respondents in the total 183 sample (23.5%); among these, sensory integration therapy (13.6%) and massage (7.1%) were 184 the most commonly used treatments. Parents in Eastern Europe also reported the highest rate 185 of use of any mind-body practices (34%); this proportion was significantly higher than rates 186 in Western (20%, p<.001), Northern (28%, p=.043) and Southern Europe (16%, p<.001). 187 Reported use of mind-body practices in Northern Europe was also significantly higher than in 188 Southern (p<.001) and Western Europe (<.006). A number of other unconventional 189 approaches not included in the previously mentioned classes of CAM were reported in 24.5% 190 of the total sample (n=514): among these, pet therapy (n= 233, 13.9%) and homeopathy 191 (n=161, 9.6%) were the most widely used. The proportion of parents reporting using such 192 10 approaches was significantly higher in Eastern Europe (43%) than in Western (24%, p<.001), 193 Northern (12%, p<.001) and Southern Europe (19%, p<.001). Reported use in Western and 194 Southern Europe was also significantly higher than in Northern Europe (p<.001 and p=.006). 195 A small minority of parents (n=40, 2.4%) reported using any invasive, disproven or 196 potentially unsafe CAM (chelation, hyperbaric chamber and packing). Rate of use of such 197 approaches was significantly higher in Eastern Europe (5%) than in Western (0.8%, p<.001), 198 Northern (1.5%, p=.006) and Southern Europe (2.5%, p=.037). The rate in Southern Europe 199 was also significantly higher than the rate in Western Europe (p=.034). The total number of 200 different CAM approaches used for those parents who used any CAM approaches ranged 201 from 1 to 12 with a mean of 2.15 (SD=1.55, IQR: 1-3) in the total sample. A significant 202 effect of European region was found on number of CAM approaches used, F (3, 785) = 9.72, 203 p<.001, ω=.18. Post hoc comparisons indicated that the mean number of approaches used 204 with children living in Eastern Europe (M = 2.60, SD = 1.87, IQR: 1-3) was significantly 205 higher than the mean number of approaches used with children living in Western Europe (M 206 = 1.92, SD = 1.40, IQR: 1-2; p<.001), Northern Europe (M = 2.06, SD = 1.22, IQR: 1-3; 207 p=.004) and Southern Europe (M = 1.93, SD = 1.42, IQR: 1-2; p<.001). 208 ----- Table 2 about here ----- 209 Predictors of CAM use 210 Logistic regression models were performed on the total sample with use of any 211 diets/supplements and use of any mind-body practice as outcome variables. Table 3 reports 212 the odds ratios and 95% CIs for the predictors of each logistic regression model. For all 213 models, the χ² statistics were significant (all p < .001) and the Hosmer & Lemeshow’s 214 goodness-of-fit tests [17] were not significant (hence indicating well-fitting models). The 215 Nagelskerke’s R 2 [27] were low (range .03-.08), which is an indication that several other 216 11 relevant variables had not been included in the model. For each predictor, the effects 217 reported below are intended to be over and above the effect of all other variables included in 218 the model. 219 ----- Table 3 ----- 220 Use of any diets/supplements 221 Use of any diets or supplements was significantly associated with low verbal ability in 222 the children and higher parental educational level. Use of prescription medication increased 223 the likelihood of using diets or supplements by 62%. Child’s gender and age and use of 224 conventional therapy were not predictors of using diets or supplements. 225 Use of any mind-body practices 226 Mind and body practices were less likely to being used with boys than with girls. A 227 higher parental educational level and high levels of use of conventional psychosocial 228 interventions were associated with concurrent use of mind-and-body practices. Child’s age 229 and verbal ability, use of medication and medium levels of use of conventional treatments 230 were not associated with use of this category of CAM. 231 Discussion 232 This study is the first to report on use of CAM in young children with autism in 233 Europe. We found that overall 47% of parents reported using at least one type of CAM or 234 other unconventional treatment in the previous 6 months. Rates of use were homogeneous 235 across Europe with the exception of significantly higher rates in Eastern Europe (66%). 236 Prevalence data from US samples obtained from reviews of patients charts vary from 30-50% 237 [21,32,1] to 70-90% [14,15]. In the total sample, parents reported using diets or supplements 238 in 24% of cases. Previous reports of use of diets ranged 27%-42% [11,13,15], but 239 12 comparisons are made difficult by the different level of detail across studies. A similar 240 proportion of parents in our total sample reported using mind-body practices (24%). Rates 241 from previous studies ranged 20-30% [15,14], but comparison should be made with caution 242 as different definitions were used or CAM approaches were considered individually rather 243 than as a class. 244 We also enquired about some invasive or potentially harmful treatments: chelation, 245 hyperbaric chamber and packing. Chelation is medical procedure involving administering 246 various chemical substances for the purpose of binding and then withdrawing specific metals 247 from the person's body; its potential serious side effects (including death) and the lack of 248 sound scientific rationale argue against its therapeutic use [6]. Hyperbaric oxygen therapy 249 involves breathing oxygen in a pressurized chamber for the purpose of increasing the amount 250 of oxygen in the blood; it is both ineffective [12] and unsafe (potential side effects include 251 paralysis and air embolism). Packing involves wrapping the individual in towels previously 252 wet in cold water to supposedly reinforce the individuals’ consciousness of their bodily 253 limits; this practice, which appears to be a clear violation of human rights, has not been 254 evaluated systematically [7]. In our sample, 40 parents (2%) reported using any of these 255 treatments with their children. 256 Among the other unconventional treatments included in the survey, it is relevant to 257 note the high prevalence of reported use of pet therapy (14%). Pet-therapy is a generic term 258 that encompasses both the use of “assistance” pets (i.e., placement of a pet in the family) and 259 the use of “therapy” pets by a therapist at home or in other settings; it is not possible to know 260 whether in our sample parents were endorsing the former or the latter. Higher figures (24%) 261 have been reported before [5]. 262 13 There were significant regional differences in the rates of use of the four over-arching 263 categories of CAM, with consistently higher rates in Eastern Europe than in the rest of 264 Europe. This might be due to lack of access to evidence-based information in those 265 countries, possibly as a residual consequence of the historical divide on health policies in 266 Europe [24] or to cultural differences in attitudes of professionals and community members 267 that are only beginning to be explored [41]. 268 We were interested in identifying correlates of use of CAM in Europe. As CAM is 269 comprised of a plethora of different types of “treatments”, we investigated correlates of use 270 of the two main classes of approaches, selected for their conceptual relevance and relative 271 homogeneity: diets and supplements and mind-body practices. No gender differences were 272 found for use of diets and supplements. There was a tendency for more mind-body practices 273 to be used with girls than with boys, but this finding should be interpreted with caution as the 274 females in the sample were only a minority (n=291, 18%). In our sample, non-verbal 275 children and children with single-words speech were more likely to being treated with diets 276 (30% increase in the probability of use), suggesting that parents of lower functioning children 277 may tend to look to a range of interventions to respond to more severe difficulties. 278 Additionally, over and above the effect of verbal ability, children using prescription 279 medication were also more likely to be treated with diets than children not using medication 280 (62% increase). Interestingly though, neither of these associations was found for use of 281 mind-body practices. This suggests that previous evidence of higher use of CAM in low 282 functioning children [32,14] might be specific to some CAM types. The association of use of 283 medication with use of diets but not mind-body practice might be due to the use of 284 supplements or alterations in the diet as an attempt to counter-balance potential side effects of 285 medications or to “boost” their efficacy [15]. Alternatively, the association could reflect 286 parental attitudes or beliefs (e.g., a generic belief in chemical/biological mechanisms) or the 287 14 willingness of the child to orally intake pills or tablets. Increased diet use in children 288 concurrently taking medications may also reflect an attempt to counteract the weight-gain 289 associated with many psychotropic medications, although we did not ask parents to report 290 why their child was on a diet, which should be done in future studies. In addition, we do not 291 have information on whether diets or supplements were medically prescribed as a treatment 292 for specific conditions (such as iron deficiency). 293 Parents with a high educational level have been consistently reported in previous 294 studies to be more likely to use CAM than parents with a lower educational level [14,1] and 295 in our study more educated parents were more likely to choose diets or supplements for their 296 child as well as using mind-and body practices. Notably, the increase in the likelihood was 297 higher for the mind-body practices (64%) than diets and supplements (35%). Mind-and-body 298 practices are practitioner-delivered and their cost is on average almost double the cost of self-299 care therapies such as supplements [28], and this might explain why in our sample mind-and-300 body practices were significantly less used by parents with a lower SES (indexed by their 301 educational level). 302 When the correlation of CAM use and use of conventional treatments has been 303 explored, it appears that availability and use of conventional treatments does not lessen use of 304 CAM. Indeed, CAM use has been found to be associated with receiving 20 or more hours 305 per week of conventional treatment [1]. Here, we explored the association between use of 306 conventional treatments and use of two specific classes of CAM. There was no association 307 between use of conventional treatment and use of diets: the use of such approaches might in 308 fact be more related to the use of medications, as suggested above. We found instead a large 309 dose-response effect of use of conventional treatments on use of mind-body practices with a 310 four-fold increase in the likelihood of concurrent CAM use for parents reporting already 311 15 using more than four conventional treatments for their child, but not for medium levels of 312 treatment (up to three interventions). 313 This finding suggests that use of mind-body practices is most strongly related with a 314 tendency to try a wide number of approaches; this might indicate that some parents, over and 315 above the effect of their child’s level of functioning (measured as verbal ability) and of their 316 own educational level (which can be constructed as a proxy of their SES), tend to look for as 317 many therapies as possible, whether these be conventional treatments or CAM approaches. 318 Use of diets appeared to be most strongly associated with lower functioning of the child and 319 concurrent use of prescription medication. 320 There is concern that desperate parents may resort to unsafe or disproven CAM 321 approaches and public agencies have been actively campaigning against them [10], but such 322 approaches were not in wide use in our sample. However, animal-assisted therapy, whose 323 efficacy is not yet established, is attracting increasing interest [30] and a considerable number 324 of parents reported using such approaches in our sample. These findings have implications 325 for clinicians and professionals involved in the care of children with ASD, in that they should 326 engage parents in frank discussions about CAM approaches, the available evidence and any 327 potential for adverse effects. 328 Strengths and limitations 329 There are a number of strengths to the present study, including the large sample size 330 and the wide scope of the survey, which enquired about the use of a range of both CAM 331 approaches and conventional treatments for young children with autism in Europe. 332 Moreover, while previous research has looked at predictive factors for use of CAM 333 considering child and parent characteristics as individual factors or only adjusting for parental 334 education level, in our study we used multiple logistic regression to estimate the contribution 335 16 of each predictor having taken into account the influence of the other factors. These findings 336 can help to identify families potentially more likely to adopt CAM approaches, and this 337 information may be beneficial both to primary care providers in their role as clinical advisors, 338 and to researchers, for example when designing trials of CAM approaches. 339 Nevertheless, the findings should be seen in the context of some limitations. Firstly, 340 we employed a recruitment method (online survey advertised via parents’ associations) that 341 might have been prone to selection bias since parents involved in associations are more likely 342 to have a relatively high income and educational level [26] and internet access is still a 343 function of socio-demographic characteristics in Europe [39]. Our sample had in fact a 344 higher than average education level [9]. However, while the recruitment strategy used 345 necessarily prevents any claims of generalizability of our results to the European population, 346 it has enabled us to reach a large number of families across Europe. Moreover, it has been 347 argued that, given the controversy around use of CAM, an anonymous online survey might 348 actually better protect against the potential risks of selection and reporting bias [36], than 349 when parents are directly asked by clinicians (as happened in most other studies on the topic). 350 Furthermore, we found that reported levels of CAM use in the present study were similar to 351 previous studies in non-EU samples. 352 The factors examined in the present study are only some of the many that might affect 353 the decision-making process underlying the choice of using CAM alongside (or alternative 354 to) conventional healthcare, which is still largely unexplained. For example, there is 355 preliminary evidence from a small sample of French parents (N=89) that personality 356 characteristics such as personal control and attribution of cause of autism affect the decision 357 to use CAM or not [2]. Parents’ own use of CAM is likely to be a relevant factor but has 358 never been examined in the association with use of CAM in children. Further research on the 359 topic should include these and other factors, such as beliefs on ASD aetiology, to better 360 17 understand the phenomenon of use of CAM for children with autism. Finally, reliance on 361 parent report in absence of direct assessments places a limitation on these findings in relation 362 to severity of child symptoms and behavioural characteristics. 363 Conclusions 364 This was the first study to report on factors associated with use of CAM in a large 365 sample of young children with autism in Europe. While little is known on the efficacy (and 366 conversely, on the potential harm) of CAM approaches, a vast amount of uncontrolled 367 information is available on-line, putting parents at risk of embarking in sometimes costly and 368 often non-efficacious treatments. Rates of CAM use, including use of disproven or unsafe 369 approaches, were particularly high in Eastern Europe. The present study contributed to the 370 understanding of the factors associated to use of CAM and provided some evidence that 371 families that tend to use a wide range of conventional treatments might also be more likely to 372 be trying some CAM approaches. The reasons behind this are not fully understood, and may 373 reflect factors that were not captured by the present study. Nonetheless these findings, taken 374 together with the evidence of socio-economic barriers in access to treatment for autism 375 [22,33, in press], provide some insight into the lengths to which families may go in pursuit of 376 ways to help their child progress. The findings highlight the need to further advance research 377 funding and policy development for evidence-based early interventions for children with 378 ASD across Europe. 379 380 381 Acknowledgements 382 We are grateful to all the parents who participated in the study and to the parent associations 383 that were involved in recruiting the participants. This research was supported by COST 384 18 Action BM1004 funded by the European Science Foundation. TC also received support from 385 the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115300, 386 resources of which are composed of financial contribution from the European Union's 387 Seventh Framework Programme (FP7/2007 - 2013) and EFPIA companies' in kind 388 contribution. It was made possible by the clinicians and researchers who are members of the 389 COST ESSEA (http://www.cost-essea.com/) and EU-AIMS (http://www.eu-aims.eu/) 390 networks. 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