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      Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

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          Abstract

          Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

            Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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              SYRCLE’s risk of bias tool for animal studies

              Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                13 May 2021
                May 2021
                : 18
                : 10
                : 5190
                Affiliations
                [1 ]Department of Psychology, Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, 43007 Tarragona, Spain; judit.biosca@ 123456urv.cat
                [2 ]Research in Neurobehavior, Health (NEUROLAB), Universitat Rovira i Virgili, 43007 Tarragona, Spain
                [3 ]Department of Psychology, Health Research Center (CEINSA), Almeria University, 04120 Almeria, Spain; cpf603@ 123456ual.es (C.P.-F.); santiagomorap@ 123456gmail.com (S.M.)
                [4 ]Department of Psychobiology, University Institute of Research-UNED-Institute of Health Carlos III (IMIENS), National Distance Education University (UNED), 28015 Madrid, Spain; bcarrillo@ 123456psi.uned.es (B.C.); hpinos@ 123456psi.uned.es (H.P.); pcollado@ 123456psi.uned.es (P.C.)
                [5 ]Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, 33011 Oviedo, Spain; conejonelida@ 123456uniovi.es (N.M.C.); jarias@ 123456uniovi.es (J.L.A.)
                [6 ]National Scholl of Public Health, Institute of Health Carlos III, University Institute of Research-UNED-Institute of Health Carlos III (IMIENS), 28029 Madrid, Spain; fmartin@ 123456isciii.es
                Author notes
                [* ]Correspondence: fsanchez@ 123456ual.es (F.S.-S.); mariateresa.colomina@ 123456urv.cat (M.T.C.)
                Author information
                https://orcid.org/0000-0001-7386-8271
                https://orcid.org/0000-0002-7393-3675
                https://orcid.org/0000-0002-5323-6602
                https://orcid.org/0000-0003-4749-5453
                https://orcid.org/0000-0002-2925-6806
                https://orcid.org/0000-0003-2190-2006
                https://orcid.org/0000-0002-5619-4874
                Article
                ijerph-18-05190
                10.3390/ijerph18105190
                8153127
                d6924c49-e8b3-48a8-9a94-a6a0b7b5972e
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 22 April 2021
                : 11 May 2021
                Categories
                Review

                Public health
                autism spectrum disorder,sociability,pesticide,organophosphate,carbamates,organochlorine,chlorpyrifos

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