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Review
, 44 (10), 277-318

Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence

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Review

Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence

Amy E Kalkbrenner et al. Curr Probl Pediatr Adolesc Health Care.

Abstract

In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.

Figures

Fig 1
Fig 1
Associations between autism and maternal smoking in pregnancy. Other results not reported as measures of association with confidence intervals included the following: Ronald et al.—small positive adjusted correlations between smoking in pregnancy and autism symptoms reported by parents and teachers—and Indredavik et al.—adjusted elevations of 1.4 points when mothers smoked during pregnancy compared to not smoking on the ASSQ, a scale with a maximum of 54 points. aAuthor provided information not included in the publication.
Fig 2
Fig 2
Associations between autism and estimates of exposure to mixed traffic and diesel air pollutants. Exposure measured during developmental windows: 1, trimester 1; 2, trimester 2; 3, trimester 3; P, pregnancy; Yr 1, 1st postnatal year. aAuthor provided information not included in the publication.
Fig 3
Fig 3
Associations between autism and estimates of exposure to individual traffic-related and criteria air pollutants. PM10, particulate matter <10 m in diameter; PM2.5, particulate matter <2.5 m in diameter; NO2, nitrogen dioxide; NO, nitrogen oxide; O3, ozone; CO, carbon monoxide. Exposure measured during developmental windows: PC, peri-conceptual; 1, trimester 1; 2, trimester 2; 3, trimester 3; P, pregnancy; Yr 1, 1st postnatal year. aWe re-calculated parameters to reflect a change in the exposure comparison to be consistent with other comparisons in the figure, involving calculations assuming that parameters were normally distributed.
Fig 4
Fig 4
Associations between autism and estimates of exposure to volatile organic compounds/solvents. Other results not reported as measures of association with confidence intervals included Kim et al.: higher retrospective reports of pregnancy exposures to “newly built homes” and “textiles” for children with autism compared to other children. VOC, volatile organic compounds; PAH7, mixed group of 7 polycyclic aromatic hydrocarbons. aAuthor provided information not included in the publication.
Fig 5
Fig 5
Associations between autism and estimates of exposure to metals from air, occupation, dental amalgams, and diet. aAuthor provided information not included in the publication. bWe re-calculated parameters to reflect a change in the exposure comparison to be consistent with other comparisons in the figure, involving calculations assuming that parameters were normally distributed.
Fig 6
Fig 6
Associations between autism and estimates of exposure to mercury from thimerosal in vaccines. RhIg, anti-D immune globulin injection; Hep B, hepatitis B vaccine; DTP, combined diphtheria, tetanus, and Pertussis vaccine; Hib, Haemophilus influenzae type B vaccine; DT, diphtheria–tetanus vaccine; aVaccine exposure measured as μg of mercury per kg of child’s body weight. bVaccine exposure measured as an index where higher numbers indicated more doses received earlier.
Fig 7
Fig 7
Associations between autism and estimates of exposure to pesticides. DE metabolites, diethyl phosphate metabolites of organophosphate pesticides; DM metabolites, dimethyl phosphate metabolites of organophosphate pesticides. Exposure measured during developmental windows: CNS, a priori period of central nervous system development (7 days pre-fertilization to 49 days postfertilization); A post., a posteriori period of development (26–81 days postfertilization); 1, trimester 1; 2, trimester 2; 3, trimester 3; P, pregnancy; Yr 1, 1st postnatal year. Other results not reported as measures of association with confidence intervals included pesticides that were determined not to be associated with increased autism risk and were not included in subsequent analyses from Roberts et al.: pesticide classes (cholinesterase inhibitors, copper-containing compounds, fumigants, avermectins, halogenated organics, N-methyl carbamates, pyrethroids, and thiocarbamates) and individual pesticide compounds (1,3-dichloropropene, chloropicrin, cypermethrin, fenarimol, methyl bromide, norflurazon, bromacil acid, chlorpyrifos, dazomet, glyphosate, molinate, oxadiazon, bifenthrin, diuron, metam-sodium, myclobutanil, and paraquat). aAuthor provided information not included in the publication. bWe re-calculated parameters to reflect a change in the exposure comparison to be consistent with other comparisons in the figure, involving calculations assuming that parameters were normally distributed.
Fig 8
Fig 8
Associations between autism and estimates of exposure to polychlorinated biphenyls, flame retardants, non-stick chemicals, phthalates, and bisphenol A. PCB, polychlorinated biphenyls; NEQ, neurotoxic equivalents, a weighted index of PCB congeners; TEQthyroid, thyroid hormone-based toxic-equivalent index of PCB congeners; BFR, brominated flame retardants, including: BB, brominated biphenyl; PBDE, polybrominated diphenyl ethers; PFC, polyfluorinated compounds (non-stick chemicals), including: PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfate; PFNA, perfluorononanoate; PFHxS, perfluorohexane sulfonate; HMW phthalates, high-molecular-weight phthalates, including: from PVC, polyvinyl chloride; MBzP, mono-benzyl phthalate; MCPP, mono-3-carboxypropyl phthalate; MECPP, mono(2-ethyl-5-carboxypentyl) phthalate; MEHHP, mono(2-ethyl-5-hydroxyhexyl) phthalate; MEHP, mono(2-ethylhexyl) phthalate; Total DEHP, di(2-ethylhexyl) phthalates = [MECPP, MEHHP, MEOHP, mono(2-ethyl-5-oxohexyl) phthalate and MEHP]; Total HMWP = MBzP and MCPP; LMW phthalates, low-molecular-weight phthalates, including: MBP, monobutyl phthalate; MEP, monoethyl phthalate; MiBP, mono-iso-butyl phthalate; MMP, monomethyl phthalate; Total LMW = MMP, MEP, MBP, MiBP. PVC Flooring A was in the child’s bedroom, PVC Flooring B was in the parents’ bedroom. Other results not reported as measures of association with confidence intervals included, for Kim et al.: higher parent report of various non-specific exposures likely to include persistent and endocrine-disrupting compounds for children with autism. aAuthor provided information not included in the publication.

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