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Research Letter
June 2017

Revisiting the Link Between Precipitation and the Risk of Autism: The Role of Environmental Nitrous Oxide Exposure

Author Affiliations
  • 1Institute of Health and Environmental Research, Cleveland, Ohio
JAMA Pediatr. 2017;171(6):596. doi:10.1001/jamapediatrics.2017.0050

Environmental factors are increasingly scrutinized regarding the etiology of autism spectrum disorders (ASD). Kinney et al1 identified a role for prenatal exposure to hurricanes in Louisiana. Their conclusion indicated that prenatal stress exposure, defined by exposure to hurricanes and tropical storms, may disrupt developmental patterns and enhance susceptibility to ASD. Important research since the work of Kinney et al,1 including novel work by Waldman et al,2 has continually implicated climatological factors, and especially state/county rainfall precipitation, in the etiology of neurodevelopmental disorders. However, while these studies acknowledge potential confounding by environmental factors, they do not address a key environmental pollutant closely related to rainfall, which is nitrous oxide (N2O). Erickson and Ayala3 provided evidence that Hurricane Georges greatly influenced N2O fluxes in the following years. The authors stated, “Emissions of N2O up to 7 months post-Georges ranged from 5.92 to 4.26 ng cm−2 h−1 and averaged 5 times greater than fluxes previously measured at the site. Nitrous oxide emissions 27 months after the hurricane remained over 2 times greater than previously measured fluxes.” Moreover, rainfall is a driver of N2O emissions.4


We propose that the primary etiological factor in the onset of neurodevelopmental disorders may be exposure to trace levels of N2O.5 We came to this conclusion from our longitudinal investigation in which we showed a possible link between using herbicide glyphosate and health care use for severe attention-deficit/hyperactivity disorder.5 Moreover, we have identified glyphosate as a possible land-dependent proxy for using nitrogen-based fertilizers, suggesting that underestimated air pollutants emanating from using anthropogenic nitrogen could be associated with a risk of neurodevelopmental disorders. Recent findings of a systematic review of case reports indicate significant psychiatric effects from N2O abuse, including psychosis.6 Another recent review on the N2O-mediated hypothesis of neurodevelopmental impairment5 highlights cognitive impairment among people exposed to low doses of N2O. Cited animal studies of prenatal N2O exposure indicate subtle differences in growth and reflex responses as well as altered body laterality, all of which are implicated in ASD.5


Should we therefore revisit the studies by Kinney et al1 and Waldman et al?2 Intriguingly, these studies point to the role of climatological factors in ASD prevalence across certain areas of the United States. Hurricanes, tropical storms, and rainfall precipitation have all increased emissions of N2O, with the effects long-lasting in some cases of extreme weather-related events. It is important to recognize that low-level exposure to N2O is thought to involve an endogenous release of opioid peptides implicated in stress adaptation, including dynorphin,5 suggesting a role for N2O as an important environmental confounder in the relationship between severe-weather related events like hurricanes and the risk of ASD among the offspring of mothers with elevated stress levels. Additionally, the level of maternal stress encountered after a hurricane is not likely to parallel that of common weather-related events like rainfall, yet both events are associated with ASD among offspring. These questions suggest that other biological mechanisms beyond stress, including glutamatergic and cholinergic dysfunction, likely contribute to the development of an ASD phenotype.5 Future work characterizing the association between weather-related events and ASD should consider the role of environmental N2O as an important etiological driver in the risk for ASD and related neuropathology.

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Article Information

Corresponding Author: Keith Fluegge, BS, Institute of Health and Environmental Research, PO Box 18442, Cleveland, OH 44118 (keithfluegge@gmail.com).

Published Online: April 10, 2017. doi:10.1001/jamapediatrics.2017.0050

Conflict of Interest Disclosures: None reported.

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Waldman  M, Nicholson  S, Adilov  N, Williams  J.  Autism prevalence and precipitation rates in California, Oregon, and Washington counties.  Arch Pediatr Adolesc Med. 2008;162(11):1026-1034.PubMedGoogle ScholarCrossref
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Li  C, Frolking  S, Frolking  TA.  A model of nitrous oxide evolution from soil driven by rainfall events, 1: model structure and sensitivity.  J Geophys Res. 1992;97(D9):9759-9776. doi:10.1029/92JD00509Google ScholarCrossref
Fluegge  K.  Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? a mini-review of the evidence.  Environ Toxicol Pharmacol. 2016;47:6-18. doi:10.1016/j.etap.2016.08.013PubMedGoogle ScholarCrossref
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