Exposição precoce a agrotóxicos de uso agrícola e ocorrência do transtorno do espectro autista: uma revisão sistemática

Bertoletti, Anna Caroline Cristofoli; Peres, Kathleen Krüger; Faccioli, Larissa Slongo; Vacci, Marina Camassola; Mata, Isabella Rosa da; Kuyven, Caroline Joana; Bosco, Simone Morelo Dal

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Revista Paulista de Pediatria

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Brasil

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Sumário

Review Article • Rev. paul. pediatr. 41 • 2023 • https://doi.org/10.1590/1984-0462/2023/41/2021360 copiar

Exposição precoce a agrotóxicos de uso agrícola e ocorrência do transtorno do espectro autista: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Objetivo:

Compreender a influência da exposição precoce a agrotóxicos de uso agrícola e sua relação com o transtorno do espectro autista.

Fontes de dados:

Esta revisão sistemática foi registrada no banco de dados PROSPERO sob número CRD42020204842. Por meio das bases de dados PubMed, Scopus e Web of Science, o assunto foi analisado sistematicamente até abril de 2021. Foram incluídos somente estudos com humanos, sendo critérios de inclusão a exposição precoce a agrotóxicos de uso agrícola e o diagnóstico de autismo e critérios de exclusão agrotóxicos de uso doméstico ou veterinário e exposição tardia. Todos os estudos foram analisados sem restrição de linguagem e tempo. A qualidade dos estudos foi avaliada pela NewCastle Ottawa Scale.

Síntese dos dados:

No total, seis estudos caso-controle foram incluídos. Três deles mensuraram a exposição pelos biomarcadores maternos e os demais (50%) pelo endereço de moradia. Os trabalhos apresentaram qualidade entre moderada e alta. Encontrou-se alta taxa de associação entre a exposição precoce à agrotóxicos e o autismo e detecção acima do limite de quantificação para amostras de bifenilas policloradas, hexaclorobenzeno e diclorodifenildicloroetileno.

Conclusões:

Existem evidências sobre a exposição a agrotóxicos de uso agrícola precocemente e o desenvolvimento do transtorno do espectro autista, porém mais pesquisas são necessárias para melhor compreensão da associação.

Palavras-chave:
Agrotóxicos; Substâncias químicas agrícolas; Transtorno do espectro autista; Exposição materna; Revisão sistemática

Author	Study population	Exposure and outcome	Results
Roberts, et al.²¹21 Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C. Maternal residence near agricultural pesticides applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007;115:1482-9. https://doi.org/10.1289/ehp.10168 https://doi.org/10.1289/ehp.10168...	Children born between 1996 and 1998, residing in the 19 countries in the Central Valley in California. Cases (n=465) and controls (n=6,975)	Home address of birth and time in pregnancy during which exposure to pesticides reported by data from the California Department of Pesticide Regulation. Children receiving services for autism or with an ASD diagnostic code.	The quantity of organochlorines for the cases suggested OR=6.1 for the ASD. When comparing the fourth quartile versus no exposure, the autism risk coefficient had associations during pregnancy with organophosphates (p=0.042), organochlorines (p=0.025), trifluralin (p=0.046), and bifenthrin (p=0.048). During the embryogenesis of the central nervous system, the results for organochlorines were attenuated with an increase in the distance from home to the application, from 250 m (p=0.001) to 1,000 m (p=0.006).
Shelton, et al.²²22 Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schimidt RJ, Ritz BT, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ Health Perspect. 2014;122:1103-9. https://doi.org/10.1289/ehp.1307044 https://doi.org/10.1289/ehp.1307044...	Children aged 2–5 years, residing in California between 1997 and 2008 with an ASD (n=486), DD (n=168), and typical development (n=316).	Home address for 3 months preconception until born, linked to the use of the California Pesticide Use Report. Previous diagnosis of ASD: ADI-R+ADOS. Typical development and DD: SCQ	Children with ASD were 60% more likely to have organophosphates applied close to the home (aOR=1.60) purchased with GC and increased for exposures in the third trimester (OR=2.0). Cases with DD had aOR = 2.48 of having carbamate pesticides applied close to home during pregnancy. Associations decreased as the size of the beam increased. Exposure to pyrethroid insecticide applications before conception or during the third trimester was at increased risk for ASD and DD (ORs 1.7–2.3).
Von Ehrenstein et al.²³23 Ehrenstein OS, Ling C, Cui X, Cockburn M, Park AS, Yu F, et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ. 2019;364:1962. https://doi.org/10.1136/bmj.l962 https://doi.org/10.1136/bmj.l962...	Individuals of any age, resident at birth, and diagnosed in California counties. Recruited between 1998 and 2010. Cases (n=296) and controls (n=35,370).	Home address at birth related to data from application reports with evaluation 3 months before pregnancy, during pregnancy, and during the first year of life. Service records are collected through regional centers and categorized by the department, using DSM-IV ed.	Stronger associations between ASD risk and exposure during the development period were for chlorpyrifos (OR=1.15), diazinon (OR = 1.14), and avermectin (OR=1.14). For ASD with ID, exposures resulted in attenuated effect estimates before and during pregnancy, while probability ratios became more pronounced for exposures in the first year of life, for glyphosate (1.60), diazinon (1.45), malathion (1.29), and bifenthrin (1.33). Exposure in the three pre-pregnancy months had weaker associations with ASD. Exposure to any pesticide substance in the first year of life brought an increase in risk for ASD combined with ID by up to 50%.

Author	Study population	Exposure and outcome	Results
Cheslack-Postava et al.¹³13 Cheslack-Postava K, Rantakokko PV, Hinkka-Yli-Salomäki S, Surcel HM, McKeague IW, Kiviranta HA, et al. Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: a pilot study. Neurotoxicol Teratol. 2013;38:1-5. https://doi.org/10.1016/j.ntt.2013.04.001 https://doi.org/10.1016/j.ntt.2013.04.00...	Children born in Finland between 1991 and 2000 (n=75 case-control pairs)	Maternal serum biomarkers (collected during the first trimester of pregnancy) analyzed by chromatography. Finnish registry with the diagnosis of ICD10 F84.0 and subsequent validation with ADI-R.	All samples, except DDT and BDE-47, were measured at levels above the LOQ. Total PCBs at or above the 90th percentile were associated with an OR=1.91 for autism.
Lyall et al.²⁰20 Lyall KL, Croen A, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, et al. Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in maternal mid-pregnancy serum samples: association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect. 2017;125:474-80. https://doi.org/10.1289/ehp277 https://doi.org/10.1289/ehp277...	Children born in three California counties between 2000 and 2003 with ASD (n=545), ID (n=181), and GP (n=418).	Samples of serum and maternal blood cell sediment (collected during 15–19 weeks of gestation) analyzed by chromatography. Previous registration and revised by MADDSP protocol. ASD classified by DSM-IV ed. With or without ID (functional cognitive test <70).	In the ASD group, the levels of PCBs and trans-nanochlorines were higher than in the CG. Increased risk of ASD mainly for PCBs 138/158, 153, 170, and 180 (aOR>1.5). The sum of PCB congeners demonstrated a moderately high risk of ASD for the upper quartile (OR=1.39). The trend tests were significant only for PCB 138/158 (p=0.03) and PCB153 (p=0.04). Increased risk of ASD for PCBs was not observed, either crude or adjusted.
Brown et al.¹⁹19 Brown A, Cheslack-Postava SK, Rantakokko P, Kiviranta H, Hinkka-Yli-Salomani S, Mc Keague IW, et al. Association of maternal insecticide levels with autism in offspring from a national birth cohort. Am J Psychiatry. 2018;175:1094-101. https://doi.org/10.1176/appi.ajp.2018.17101129 https://doi.org/10.1176/appi.ajp.2018.17...	Children born in Finland between 1987 and 2005 (n=778 case-control pairs).	Maternal serum biomarkers (collected between 2 and 4 months of pregnancy) analyzed by chromatography. Hospital record with diagnosis of ICD10 F84.0 and validation with the Autism Diagnostic Interview.	p,p’-DDE was measured in an amount greater than the LOQ in all samples. Among similar PCBs, it was measured above the LOQ between 95% and 100% of the samples. Increased chances of autism in offspring when maternal levels of p,p’-DDE in the 75th percentile (OR=1.32 and p=0.03), male (OR=1.35 and p=0.04), and also individuals with intellectual disabilities (OR=2.21 and p=0.002). No association was observed for PCB 138 or PCB 153 as well as the other total PCBs, congeners, and autism.

Study	Selection	Comparability	Exposure	Total
Roberts et al.²¹21 Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C. Maternal residence near agricultural pesticides applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007;115:1482-9. https://doi.org/10.1289/ehp.10168 https://doi.org/10.1289/ehp.10168...	**	*	**	5
Shelton et al.²²22 Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schimidt RJ, Ritz BT, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ Health Perspect. 2014;122:1103-9. https://doi.org/10.1289/ehp.1307044 https://doi.org/10.1289/ehp.1307044...	****	*	**	7
Von Ehrenstein et al.²³23 Ehrenstein OS, Ling C, Cui X, Cockburn M, Park AS, Yu F, et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ. 2019;364:1962. https://doi.org/10.1136/bmj.l962 https://doi.org/10.1136/bmj.l962...	**	**	**	6
Cheslack-Postava et al.¹³13 Cheslack-Postava K, Rantakokko PV, Hinkka-Yli-Salomäki S, Surcel HM, McKeague IW, Kiviranta HA, et al. Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: a pilot study. Neurotoxicol Teratol. 2013;38:1-5. https://doi.org/10.1016/j.ntt.2013.04.001 https://doi.org/10.1016/j.ntt.2013.04.00...	**	**	**	6
Lyall et al.²⁰20 Lyall KL, Croen A, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, et al. Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in maternal mid-pregnancy serum samples: association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect. 2017;125:474-80. https://doi.org/10.1289/ehp277 https://doi.org/10.1289/ehp277...	***	**	***	8
Brown et al.¹⁹19 Brown A, Cheslack-Postava SK, Rantakokko P, Kiviranta H, Hinkka-Yli-Salomani S, Mc Keague IW, et al. Association of maternal insecticide levels with autism in offspring from a national birth cohort. Am J Psychiatry. 2018;175:1094-101. https://doi.org/10.1176/appi.ajp.2018.17101129 https://doi.org/10.1176/appi.ajp.2018.17...	***	*	**	6

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[1] *Corresponding author. E-mail: simonedb@ufcspa.edu.br (S. M. Dal Bosco).