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

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.

Autism Spectrum Disorder and Prenatal or Early Life Exposure to Pesticides: A Short Review

“…The results of this review, relating to the maternal exposure to organophosphate in pregnancy or in the first years of a child's life and the risk of ASD onset, confirm the findings presented in a recent systematic review of human and preclinical models, which suggested that the gestational exposure to certain organophosphate agents could be linked to the clinical signs of ASD [18].…”

“…The number of articles included in our review is small because we have specifically chosen to consider only the cohort and case-control studies involving humans and those which take into account the diagnoses of ASD in children based on the most recent diagnostic tools: DSM IV and V (Diagnostic and Statistical Manual of Mental Disorders, fourth edition and Diagnostic and Statistical Manual of Mental Disorders). On the contrary, other reviews that included a higher number of papers also considered in vitro and animal studies [18]. Increasing the number of studies included in a future meta-analysis could help to improve the statistical power and highlight the possible associations between the onset of ASD and the exposure to atmospheric pollutants.…”

“…Several experimental and epidemiological studies have highlighted the association between neurodevelopmental disorders and pre/postnatal or chronic exposure to pesticides. In addition, a recent systematic review of human and preclinical models has suggested that the gestational exposure to certain organophosphate agents could be linked to the clinical signs of ASD [18]. The aim of this review of studies carried out up until 2020 is to perform a descriptive analysis of any association that has been found between the use of pesticides (to which most of the world's population is exposed) and autism spectrum disorder, summarizing at the same time the different covariates examined, the type of statistical analysis performed and the possible factors that could affect this relationship.…”

Machine learning assisted discovery of synergistic interactions between environmental pesticides, phthalates, phenols, and trace elements in child neurodevelopment

“…It is commonly found in the food chain, soil, cigarette smoke, and manufactured products 73 . Research on pesticide exposure during childhood, specifically glyphosate 76, 77 , chlorpyrifos 77 , diazinon 77 , and the development of ASD continues to emerge 78-80 . Potential routes of pesticide exposure in children include food contaminated with pesticides (ingestion), in utero or through breastmilk, and household exposures via dermal contact 81, 82 .…”

Investigation of Prenatal Pesticide Exposure and Neurodevelopmental Deficits in Northern Thailand: Protocol for a Longitudinal Birth Cohort Study

“…Prenatal exposure to mixtures of neurotoxic pesticides is prevalent worldwide and has the potential to disrupt and irreversibly alter neurologic development [ 1 - 3 ]. In 2017, approximately 8.8 billion pounds of pesticides were used worldwide [ 4 ].…”