{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T04:53:54Z","timestamp":1769230434805,"version":"3.49.0"},"reference-count":35,"publisher":"FapUNIFESP (SciELO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq. Neuro-Psiquiatr."],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>ABSTRACT The link between various air pollutants and hospitalization for epilepsy has come under scrutiny. We have proposed that exposure to air pollution and specifically the pervasive agricultural air pollutant and greenhouse gas, nitrous oxide (N2O), may provoke susceptibility to neurodevelopmental disorders. Evidence supports a role of N2O exposure in reducing epileptiform seizure activity, while withdrawal from the drug has been shown to induce seizure-like activity. Therefore, we show here that the statewide use of anthropogenic nitrogen fertilizers (the most recognized causal contributor to environmental N2O burden) is significantly negatively associated with hospitalization for epilepsy in all three pre-specified hospitalization categories, even after multiple pollutant comparison correction (p&lt;.007), while the other identified pollutants were not consistently statistically significantly associated with hospitalization for epilepsy. We discuss potential neurological mechanisms underpinning this association between air pollutants associated with farm use of anthropogenic nitrogen fertilizers and hospitalization for epilepsy.<\/jats:p>","DOI":"10.1590\/0004-282x20170107","type":"journal-article","created":{"date-parts":[[2017,9,23]],"date-time":"2017-09-23T19:28:17Z","timestamp":1506194897000},"page":"614-619","source":"Crossref","is-referenced-by-count":19,"title":["Air pollution and risk of hospitalization for epilepsy: the role of farm use of nitrogen fertilizers and emissions of the agricultural air pollutant, nitrous oxide"],"prefix":"10.1590","volume":"75","author":[{"given":"Keith","family":"Fluegge","sequence":"first","affiliation":[{"name":"Institute of Health and Environmental Research,  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Fluegge","sequence":"additional","affiliation":[{"name":"Institute of Health and Environmental Research,  USA; New York City Department of Health and Mental Hygiene,  USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","reference":[{"issue":"10","key":"ref1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1590\/0004-282X20130092","article-title":"Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy","volume":"71","author":"Scorza CA","year":"2013","journal-title":"Arq Neuropsiquiatr"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.envint.2010.03.008","article-title":"Air pollution and hospitalization for epilepsy in Chile","volume":"36","author":"Cakmak S","year":"2010","journal-title":"Environ Int"},{"issue":"8","key":"ref3","article-title":"The novel relationship between urban air pollution and epilepsy: a time series study","volume":"11","author":"Xu C","year":"2016","journal-title":"PLoS One"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1179\/1743132814Y.0000000445","article-title":"Ozone protective effects against PTZ-induced generalized seizures are mediated by reestablishment of cellular redox balance and A1 adenosine receptors","volume":"37","author":"Mallok A","year":"2015","journal-title":"Neurol Res"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.aogh.2015.06.008","article-title":"Chile confronts its environmental health future after 25 years of accelerated growth","volume":"81","author":"Pino P","year":"2015","journal-title":"Ann Glob Health"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.etap.2016.08.013","article-title":"Does environmental exposure to the greenhouse gas, N2O, contribute to etiological factors in neurodevelopmental disorders? A mini-review of the evidence","volume":"47","author":"Fluegge K","year":"2016","journal-title":"Environ Toxicol Pharmacol"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.15244\/pjoes\/61742","article-title":"Glyphosate use predicts healthcare utilization for ADHD in the Healthcare Cost and Utilization Project net (HCUPnet): a two-way fixed-effects analysis","volume":"25","author":"Fluegge K","year":"2016","journal-title":"Pol J Environ Stud"},{"issue":"23","key":"ref8","doi-asserted-by":"crossref","first-page":"24416","DOI":"10.1007\/s11356-016-7837-0","article-title":"Polycyclic aromatic hydrocarbons and child mental health: is the effect modified by exposure to environmental nitrous oxide?","volume":"23","author":"Fluegge K","year":"2016","journal-title":"Environ Sci Pollut Res Int"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.envint.2017.02.012","article-title":"Exposure to ambient PM10 and nitrogen dioxide and ADHD risk: a reply to Min & Min (2017)","volume":"103","author":"Fluegge K","year":"2017","journal-title":"Environ Int"},{"issue":"2","key":"ref10","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2015-4654","article-title":"Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD","volume":"138","author":"Bertelsen EN","year":"2016","journal-title":"Pediatrics"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1212\/WNL.0000000000002836","article-title":"Autism and epilepsy: A population-based nationwide cohort study","volume":"87","author":"Sundelin HE","year":"2016","journal-title":"Neurology"},{"key":"ref12","first-page":"287","article-title":"Epilepsy and attention-deficit hyperactivity disorder: links, risks, and challenges","volume":"12","author":"Williams AE","year":"2016","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"3","key":"ref13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/00008506-199009000-00006","article-title":"Nitrous oxide: suppression of focal epileptiform activity during inhalation, and spreading of seizure activity following withdrawal","volume":"2","author":"Artru AA","year":"1990","journal-title":"J Neurosurg Anesthesiol"},{"issue":"17","key":"ref14","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/0024-3205(87)90477-2","article-title":"Ethanol and nitrous oxide produce withdrawal-induced convulsions by similar mechanisms in mice","volume":"41","author":"Belknap JK","year":"1987","journal-title":"Life Sci"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1213\/00000539-198001000-00004","article-title":"Withdrawal convulsions in mice following nitrous oxide","volume":"59","author":"Harper MH","year":"1980","journal-title":"Anesth Analg"},{"issue":"6","key":"ref16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1097\/00000542-197906000-00005","article-title":"Convulsions in mice after anesthesia","volume":"50","author":"Smith RA","year":"1979","journal-title":"Anesthesiology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.yebeh.2016.02.009","article-title":"Does the association between ADHD and pediatric epilepsy signal a tolerance continuum to human environmental exposures? A reply to Salpekar and Mishra (2014)","volume":"58","author":"Fluegge K","year":"2016","journal-title":"Epilepsy Behav"},{"issue":"4","key":"ref18","doi-asserted-by":"crossref","first-page":"044017","DOI":"10.1088\/1748-9326\/10\/4\/044017","article-title":"Presence of nitrous oxide hotspots in the coastal upwelling area off central Chile: an analysis of temporal variability based on ten years of a biogeochemical time series","volume":"10","author":"Far\u00edas L","year":"2015","journal-title":"Environ Res Lett"},{"issue":"25","key":"ref19","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.1073\/pnas.1322434111","article-title":"Global metaanalysis of the nonlinear response of soil nitrous oxide (N2O) emissions to fertilizer nitrogen","volume":"111","author":"Shcherbak I","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref20","article-title":"County-level estimates of nitrogen and phosphorus from commercial fertilizer for the Conterminous United States, 1987\u20132006","volume":"5207","author":"Gronberg JM","year":"2012","journal-title":"U US Geol Surv Sci Investig Rep"},{"key":"ref21","article-title":"Estimation of annual agricultural pesticide use for counties of the conterminousUnited States, 1992\u20132009","volume":"5009","author":"Thelin GP","year":"2013","journal-title":"US Geol Surv Sci Investig Rep"},{"key":"ref22","series-title":"EPA disclaimers","year":"2016"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","DOI":"10.1186\/s12940-016-0208-y","article-title":"Influence of exposure differences on city-to-city heterogeneity in PM2.5-mortality associations in US cities","volume":"16","author":"Baxter LK","year":"2017","journal-title":"Environ Health"},{"key":"ref24","series-title":"Daily summary data: criteria gases","year":"2014"},{"key":"ref25","series-title":"Healthcare Cost and Utilization Project (HCUPNET): state inpatient database","year":"2014"},{"key":"ref26","first-page":"56","article-title":"Air pollution and forests: interaction between air contaminants and forest ecosystems","author":"Smith WH","year":"1981","journal-title":"Forests as sinks for air contaminants: soil compartment"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1146\/annurev.publhealth.23.100901.140516","article-title":"The future of benefit-cost analyses of the Clean Air Act","volume":"23","author":"Krupnick A","year":"2002","journal-title":"Annu Rev Public Health"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.seizure.2016.12.009","article-title":"Stress as a seizure precipitant: Identification, associated factors, and treatment options","volume":"44","author":"McKee HR","year":"2017","journal-title":"Seizure"},{"issue":"5","key":"ref29","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nn.2790","article-title":"Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy","volume":"14","author":"Huberfeld G","year":"2011","journal-title":"Nat Neurosci"},{"issue":"5949","key":"ref30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1126\/science.1176985","article-title":"Nitrous oxide (N2O): the dominant ozone-depleting substance emitted in the 21st century","volume":"326","author":"Ravishankara AR","year":"2009","journal-title":"Science"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2134\/jeq2003.4230","article-title":"Nitrous oxide, nitric oxide, and nitrogen dioxide fluxes from soils after manure and urea application","volume":"32","author":"Akiyama H","year":"2003","journal-title":"J Environ Qual"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1073\/pnas.1011464108","article-title":"Nitrous oxide emission from denitrification in stream and river networks","volume":"108","author":"Beaulieu JJ","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"32","key":"ref33","doi-asserted-by":"crossref","first-page":"9839","DOI":"10.1073\/pnas.1503598112","article-title":"Indirect nitrous oxide emissions from streams within the US Corn Belt scale with stream order","volume":"112","author":"Turner PA","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4067\/S0718-58392016000100012","article-title":"Diurnal pattern of nitrous oxide emissions from soils under different vertical moisture distribution conditions","volume":"76","author":"Xu J","year":"2016","journal-title":"Chil J Agric Res"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1212\/WNL.0b013e3181ae7ca6","article-title":"Why do seizures in generalized epilepsy often occur in the morning?","volume":"73","author":"Badawy RA","year":"2009","journal-title":"Neurology"}],"container-title":["Arquivos de Neuro-Psiquiatria"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/pdf\/anp\/v75n9\/0004-282X-anp-75-09-0614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T18:05:59Z","timestamp":1508349959000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0004-282X2017000900614&lng=en&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["S0004-282X2017000900614"],"URL":"https:\/\/doi.org\/10.1590\/0004-282x20170107","relation":{},"ISSN":["0004-282X"],"issn-type":[{"value":"0004-282X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9]]}}}