Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

Introduction: Some recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs. Methods: We performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility. Results: We found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro. The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence). The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect. Conclusions: We found the administration of PUFAs in children and adolescents with ASD to be potentially equitable, acceptable and feasible. These results are limited by the limited number and quality of retrieved documents, and need to be viewed in light of efficacy and safety data to formulate clinical recommendations.</br

Impact of polyunsaturated fatty acids on patient-important outcomes in children and adolescents with autism spectrum disorder: A systematic review

Background: Recent randomized controlled trials (RCTs) claimed PUFAs to be effective for autism spectrum disorder (ASD) but international guidelines have not considered yet this body of evidence. Our aim was to assess the effectiveness of PUFAs in children and adolescents with ASD, for the Italian national guidelines on the management of ASD in children and adolescents. Methods: We performed a systematic review and meta-analysis of RCTs comparing PUFAs versus placebo or a healthy diet for the treatment of ASD in children and adolescents. The outcomes considered were deemed by the guideline panel to be highly relevant to children and adolescents with ASD and to their caregivers. The outcomes included hyperactivity, quality of sleep, self-harm, aggression, irritability, anxiety, attention, adaptive functioning, social interaction, restricted and repetitive interests and behavior, communication, hyperactivity and disruptive behaviors coexistent with core symptoms. The risk of bias of the included studies was assessed with the Cochrane tool, and the rating of the confidence in the effect estimates according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: We included 9 studies with 405 participants. The strength of evidence ranged from low to very low. Six studies included preschoolers and school-age children, three studies included both children and adolescents. The majority of participants were males (83.8%), with a mean age of 6.7 years. PUFAs were superior compared to placebo in reducing anxiety in individuals with ASD (SMD -1.01, 95% CI − 1.86 to − 0.17; very low certainty of evidence). Moreover, PUFAs worsened quality of sleep compared to a healthy diet (SMD 1.11, 95% CI 0.21 to 2.00; very low certainty of evidence). PUFAs were not better than placebo in reducing aggression, hyperactivity, adaptive functioning, irritability, restricted and repetitive interests and behaviors and communication. Effects on some critical outcomes such as sleep, self-harm and disruptive behavior are currently unknown. The main limitations were the small number of participants included in the RCTs and the dosage which varied greatly (from 200 mg/day to 1540 mg/day), making it difficult to address causal inference. Conclusions: PUFAs did not show evidence of effect in children and adolescents with ASD and the certainty of evidence as measured with the GRADE was low to very low. Further research is needed on this topic because the available evidence is inconclusive.</p