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Vol. 93. Issue 3.
Pages 308-309 (May - June 2017)
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Vol. 93. Issue 3.
Pages 308-309 (May - June 2017)
Letter to the Editor
Open Access
Autism in 2016: additional discovery
Autismo em 2016: descoberta adicional
Keith Fluegge
Institute of Health and Environmental Research, Cleveland, United States
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J Pediatr (Rio J). 2017;93:309-1010.1016/j.jped.2016.12.002
Annio Posar, Paola Visconti
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To the Editor,

Posar and Visconti1 have recently published their narrative biomedical review on the developments in the field of autism research in 2016, with a particular focus on the hypothetical role of environmental factors, like air pollution. The authors searched the available recent literature using PubMed (United States National Library of Medicine) for interesting hypotheses published between January 1, 2013 and August 20, 2016 and relevant literature (case–control studies involving human participants were preferred) using a variety of selected keywords. Although the authors identified a search strategy, their review did not consider a recently published mini-review identifying the role of the specific agricultural air pollutant, nitrous oxide (N2O), in autism etiopathogenesis and neurodevelopmental disorders more broadly.

Fluegge2 has suggested repeatedly that exposure to environmental N2O may increase susceptibility to a range of neurodevelopmental disorders, including autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). An initial epidemiological analysis revealed an association between the use of the pesticide glyphosate and ADHD, but subsequent sensitivity analyses found that the association was likely dependent upon the level of land urbanization and glyphosate's strong county-specific association with nitrogen-based fertilizers and presumable emissions of N2O.2 These findings were replicated in an analysis of ASD hospitalizations (personal communication). Hypothesized mechanisms of interest underlying these associations included known pharmacological targets of low level N2O exposure, including NMDA receptor antagonism (N-methyl-d-aspartate receptor), stimulation of central opioid peptide release, and suppression of cholinergic activity.3 The review is particularly notable since environmental N2O has not been considered by either Posar and Visconti1 or the studies that comprise their narrative review as an air pollutant capable of inducing adverse human health consequences and autism, in particular. It is, therefore, interesting to read the authors’ suggestion to investigate whether there is a difference in autism prevalence among nations exposed to low vs. high levels of pollution.

Tian et al.4 recently reported on the annual rates of change for a multitude of environmental factors for different continents, having found significant increases in nitrogen fertilizer use in North America from 1981 to 2010 and significant decreases in nitrogen fertilizer use in Europe during the same period. As the use of anthropogenic nitrogen sources is the most directly tied environmental contributor to N2O emissions,5 this continental difference in nitrogen fertilizer use going back decades is particularly revealing and suggests higher U.S. emissions of N2O derived from nitrogen fertilizers compared to Europe, a fact confirmed by the Intergovernmental Panel on Climate Change (IPCC, 2015).6 This geographical distinction could explain the differential dynamics in ASD prevalence.

Epidemiologic, population-based studies from Europe indicate that much of the increase in ASD prevalence between 1980 and 2003 can be accounted for by changes in administrative and reporting practices,7,8 while ASD prevalence in the subsequent years in the UK may have plateaued.9 These data argue for the possibility that the increase in the registered prevalence of ASD may be driven more by administrative changes. However, the marked increase in ASD prevalence in the United States between 2000 and 2012, in particular, could not be readily accounted for by any evolution in diagnostic criteria since no formal changes were introduced or adopted during this time, although it cannot be discounted that the increasing prevalence of ASD during this time might be attributable to lingering diagnostic substitution or the accrual of practices started in the prior decades.10 This, therefore, leaves open the possibility that secular environmental contributors, like environmental N2O, may play a role in ASD etiopathogenesis in a continentally distinct way. In light of this research, Posar and Visconti1 may wish to expand their view on the role of air pollution as a risk factor in ASD. Considering that N2O is not regarded as a human health pollutant in the literature or by government officials, a call for a re-evaluation of this particular environmental pollutant seems necessary.

Conflicts of interest

The author declares no conflicts of interest.

A. Posar, P. Visconti.
Autism in 2016: the need for answers.
J Pediatr (Rio J), 93 (2017), pp. 111-119
K.R. Fluegge, K.R. Fluegge.
Glyphosate use predicts ADHD hospital discharges in the Healthcare Cost and Utilization Project Net (HCUPnet): a two-way fixed-effects analysis.
PLoS One, 10 (2015), pp. e0133525
K. Fluegge.
Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini-review of the evidence.
Environ Toxicol Pharmacol, 47 (2016), pp. 6-18
H. Tian, G. Chen, C. Lu, X. Xu, W. Ren, B. Zhang, et al.
Global methane and nitrous oxide emissions from terrestrial ecosystems due to multiple environmental changes.
Ecosyst Health Sustain, 1 (2015), pp. 1-20
S. Park, P. Croteau, K.A. Boering, D.M. Etheridge, D. Ferretti, P.J. Fraser, et al.
Trends and seasonal cycles in the isotopic composition of nitrous oxide since 1940.
Nat Geosci, 5 (2012), pp. 261-265
Intergovernmental Panel on Climate Change (IPCC). Climate Change 2001: Mitigation [cited 4 July 2016]. Available from:
S. Lundström, A. Reichenberg, H. Anckarsäter, P. Lichtenstein, C. Gillberg.
Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples.
BMJ, 350 (2015), pp. h1961
S.N. Hansen, D.E. Schendel, E.T. Parner.
Explaining the increase in the prevalence of autism spectrum disorders: the proportion attributable to changes in reporting practices.
JAMA Pediatr, 169 (2015), pp. 56-62
B. Taylor, H. Jick, D. Maclaughlin.
Prevalence and incidence rates of autism in the UK: time trend from 2004–2010 in children aged 8 years.
BMJ Open, 3 (2013), pp. e003219
Committee to Evaluate the Supplemental Security Income Disability Program for Children with Mental Disorders; Board on the Health of Select Populations; Board on Children, Youth, and Families; Institute of Medicine; Division of Behavioral and Social Sciences and Education; The National Academies of Sciences, Engineering, and Medicine; Boat TF, Wu JT, eds. Mental disorders and disabilities among low-income children. Washington (DC): National Academies Press (US). 14, Prevalence of autism spectrum disorder. [cited 4 July 2016]. Available from:

Please cite this article as: Fluegge K. Autism in 2016: additional discovery. J Pediatr (Rio J). 2017;93:308–9.

Copyright © 2016. Sociedade Brasileira de Pediatria
Jornal de Pediatria (English Edition)

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