Abstract
This meta-analysis was conducted to estimate the overall association between maternal exposure to pesticides and risk of ASD in offspring. PubMed, EMBASE, Web of Science, and the PsycINFO were searched until December 30, 2020 to include eligible studies. Eight studies with 50,426 participants, 5810 of whom had ASD, were involved in the study. Overall, the summary OR (95% confidence interval) of ASDs in offspring for maternal exposure to pesticide estimated by residential proximity measures and self-report was 1.88 (1.10–3.20). However, maternal exposure to pesticide measured by biomarkers was not associated with an increased risk of ASDs (pooled OR 1.13; 95% CI 0.83–1.54). Further well-designed studies are needed to confirm our findings.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Psychiatric Association (APA). (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th ed. American Psychiatric Association. Retrieved April 4, 2020, from https://www.psychiatry.org/psychiatrists/practice/dsm
Andersen, H. R., Debes, F., Wohlfahrt-Veje, C., Murata, K., & Grandjean, P. (2015). Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age. Neurotoxicology and Teratology, 47, 1–9. https://doi.org/10.1016/j.ntt.2014.10.006
Bachelet, D., Truong, T., Verner, M.-A., Arveux, P., Kerbrat, P., Charlier, C., Guihenneuc-Jouyaux, C., & Guénel, P. (2011). Determinants of serum concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls among French women in the CECILE study. Environmental Research, 111, 861–870. https://doi.org/10.1016/j.envres.2011.06.001
Baxter, A. J., Brugha, T. S., Erskine, H. E., Scheurer, R. W., Vos, T., & Scott, J. G. (2015). The epidemiology and global burden of autism spectrum disorders. Psychological Medicine, 45, 601–613. https://doi.org/10.1017/s003329171400172x
Begg, C. B., & Mazumdar, M. (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088–1101
Bigbee, J. W., Sharma, K. V., Chan, E. L. P., & Bögler, O. (2000). Evidence for the direct role of acetylcholinesterase in neurite outgrowth in primary dorsal root ganglion neurons. Brain Research, 861, 354–362. https://doi.org/10.1016/S0006-8993(00)02046-1
Bjørklund, G., Meguid, N. A., El-Bana, M. A., Tinkov, A. A., Saad, K., Dadar, M., Hemimi, M., Skalny, A. V., Hosnedlová, B., Kizek, R., Osredkar, J., Urbina, M. A., Fabjan, T., El-Houfey, A. A., Kałużna-Czaplińska, J., Gątarek, P., & Chirumbolo, S. (2020). Oxidative stress in autism spectrum disorder. Molecular Neurobiology. https://doi.org/10.1007/s12035-019-01742-2
Bradman, A., Barr, D. B., Claus Henn, B. G., Drumheller, T., Curry, C., & Eskenazi, B. (2003). Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: A validation study. Environmental Health Perspectives, 111, 1779–1782. https://doi.org/10.1289/ehp.6259
Brown, A. S., Cheslack-Postava, K., Rantakokko, P., Kiviranta, H., Hinkka-Yli-Salomäki, S., McKeague, I. W., Surcel, H.-M., & Sourander, A. (2018). Association of maternal insecticide levels with autism in offspring from a national birth cohort. American Journal of Psychiatry, 175, 1094–1101. https://doi.org/10.1176/appi.ajp.2018.17101129
Burdorf, A., Brand, T., Jaddoe, V. W., Hofman, A., Mackenbach, J. P., & Steegers, E. A. P. (2011). The effects of work-related maternal risk factors on time to pregnancy, preterm birth and birth weight: The generation R study. Occupational and Environmental Medicine, 68, 197. https://doi.org/10.1136/oem.2009.046516
Casida, J. E. (2009). Pest toxicology: The primary mechanisms of pesticide action. Chemical Research in Toxicology, 22, 609–619. https://doi.org/10.1021/tx8004949
Cheslack-Postava, K., Rantakokko, P. V., Hinkka-Yli-Salomäki, S., Surcel, H.-M., McKeague, I. W., Kiviranta, H. A., Sourander, A., & Brown, A. S. (2013). Maternal serum persistent organic pollutants in the finnish prenatal study of autism: A pilot study. Neurotoxicology and Teratology, 38, 1–5. https://doi.org/10.1016/j.ntt.2013.04.001
Christian, M. A., Samms-Vaughan, M., Lee, M., Bressler, J., Hessabi, M., Grove, M. L., Shakespeare-Pellington, S., Desai, C. C., Reece, J.-A., Loveland, K. A., Boerwinkle, E., & Rahbar, M. H. (2018). Maternal exposures associated with autism spectrum disorder in Jamaican children. Journal of Autism and Developmental Disorders, 48, 2766–2778. https://doi.org/10.1007/s10803-018-3537-6
de Bildt, A., Sytema, S., Ketelaars, C., Kraijer, D., Mulder, E., Volkmar, F., & Minderaa, R. (2004). Interrelationship between autism diagnostic observation schedule-generic (ADOS-G), autism diagnostic interview-revised (ADI-R), and the diagnostic and statistical manual of mental disorders (DSM-IV-TR) classification in children and adolescents with mental retardation. Journal of Autism and Developmental Disorders, 34, 129–137. https://doi.org/10.1023/B:JADD.0000022604.22374.5f
De Felice, A., Scattoni, M. L., Ricceri, L., & Calamandrei, G. (2015). Prenatal exposure to a common organophosphate insecticide delays motor development in a mouse model of idiopathic autism. PLoS ONE, 10, e0121663. https://doi.org/10.1371/journal.pone.0121663
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629. https://doi.org/10.1136/bmj.315.7109.629
Eskenazi, B., Marks, A. R., Bradman, A., Harley, K., Barr, D. B., Johnson, C., Morga, N., & Jewell, N. P. (2007). Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environmental health perspectives, 115, 792–8. https://doi.org/10.1289/ehp.9828
Evangelou, E., Ntritsos, G., Chondrogiorgi, M., Kavvoura, F. K., Hernández, A. F., Ntzani, E. E., & Tzoulaki, I. (2016). Exposure to pesticides and diabetes: A systematic review and meta-analysis. Environment International, 91, 60–68. https://doi.org/10.1016/j.envint.2016.02.013
Furlong, M. A., Engel, S. M., Barr, D. B., & Wolff, M. S. (2014). Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood. Environment International, 70, 125–131. https://doi.org/10.1016/j.envint.2014.05.011
Gray, L. E., Jr., & Ostby, J. (1998). Effects of pesticides and toxic substances on behavioral and morphological reproductive development: Endocrine versus nonendocrine mechanisms. Toxicology and Industrial Health, 14, 159–184. https://doi.org/10.1177/074823379801400111
Hamra, G. B., Lyall, K., Windham, G. C., Calafat, A. M., Sjödin, A., Volk, H., & Croen, L. A. (2019). Prenatal exposure to endocrine-disrupting chemicals in relation to autism spectrum disorder and intellectual disability. Epidemiology (Cambridge, Mass), 30, 418–426. https://doi.org/10.1097/ede.0000000000000983
Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21, 1539–1558. https://doi.org/10.1002/sim.1186
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557. https://doi.org/10.1136/bmj.327.7414.557
Keil, A. P., Daniels, J. L., & Hertz-Picciotto, I. (2014). Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: The CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Environmental Health : A Global Access Science Source, 13, 3. https://doi.org/10.1186/1476-069x-13-3
Landrigan, P. (2017). Pesticides and human reproduction. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2017.5092
Lee, D.-H., Lind, L., Jacobs, D. R., Salihovic, S., van Bavel, B., & Lind, P. M. (2012). Associations of persistent organic pollutants with abdominal obesity in the elderly: The prospective investigation of the vasculature in uppsala seniors (PIVUS) study. Environment International, 40, 170–178. https://doi.org/10.1016/j.envint.2011.07.010
Lee, I., Eriksson, P., Fredriksson, A., Buratovic, S., & Viberg, H. (2015). Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin. Toxicology, 335, 1–10. https://doi.org/10.1016/j.tox.2015.06.010
Lord, C., Brugha, T. S., Charman, T., Cusack, J., Dumas, G., Frazier, T., Jones, E. J. H., Jones, R. M., Pickles, A., State, M. W., Taylor, J. L., & Veenstra-VanderWeele, J. (2020). Autism spectrum disorder. Nature Reviews Disease Primers, 6, 5. https://doi.org/10.1038/s41572-019-0138-4
Lu, C., Bravo, R., Caltabiano, L. M., Irish, R. M., Weerasekera, G., & Barr, D. B. (2005). The presence of dialkylphosphates in fresh fruit juices: Implication for organophosphorus pesticide exposure and risk assessments. Journal of Toxicology and Environmental Health, Part A, 68, 209–227. https://doi.org/10.1080/15287390590890554
Lyall, K., Croen, L. A., Sjödin, A., Yoshida, C. K., Zerbo, O., Kharrazi, M., & Windham, G. C. (2017). Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: Association with autism spectrum disorder and intellectual disability. Environmental Health Perspectives, 125, 474–480. https://doi.org/10.1289/EHP277
Morales, D. R., Slattery, J., Evans, S., & Kurz, X. (2018). Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: Systematic review of observational studies and methodological considerations. BMC Medicine, 16, 6. https://doi.org/10.1186/s12916-017-0993-3
Mostafalou, S., & Abdollahi, M. (2017). Pesticides: An update of human exposure and toxicity. Archives of Toxicology, 91, 549–599. https://doi.org/10.1007/s00204-016-1849-x
World Health Organization. (2019). Fact sheet, autism spectrum disorders. World Health Organization, Retrieved April 4, 2020, from https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders
Pang, Y., Lee, C. M., Wright, M., Shen, J., Shen, B., & Bo, J. (2018). Challenges of case identification and diagnosis of autism spectrum disorders in China: A critical review of procedures, assessment, and diagnostic criteria. Research in Autism Spectrum Disorders, 53, 53–66. https://doi.org/10.1016/j.rasd.2018.06.003
Pearson, B. L., Simon, J. M., McCoy, E. S., Salazar, G., Fragola, G., & Zylka, M. J. (2016). Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration. Nature Communications, 7, 11173. https://doi.org/10.1038/ncomms11173
Philippat, C., Barkoski, J., Tancredi, D. J., Elms, B., Barr, D. B., Ozonoff, S., Bennett, D. H., & Hertz-Picciotto, I. (2018). Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a high-risk cohort. International Journal of Hygiene and Environmental Health, 221, 548–555. https://doi.org/10.1016/j.ijheh.2018.02.004
Roberts Eric, M., English Paul, B., Grether Judith, K., Windham Gayle, C., Somberg, L., & Wolff, C. (2007). Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the california central valley. Environmental Health Perspectives, 115, 1482–1489. https://doi.org/10.1289/ehp.10168
Ruediger, T., & Bolz, J. (2007). Neurotransmitters and the development of neuronal circuits. Advances in Experimental Medicine and Biology, 621, 104–115. https://doi.org/10.1007/978-0-387-76715-4_8
Sagiv, S. K., Harris, M. H., Gunier, R. B., Kogut, K. R., Harley, K. G., Deardorff, J., Bradman, A., Holland, N., & Eskenazi, B. (2018). Prenatal organophosphate pesticide exposure and traits related to autism spectrum disorders in a population living in proximity to agriculture. Environmental Health Perspectives, 126, 047012. https://doi.org/10.1289/ehp2580
Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing maternal age is associated with increasing risk for autism: A review and meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 51, 477-486.e1. https://doi.org/10.1016/j.jaac.2012.02.018
Schmidt, R. J., Kogan, V., Shelton, J. F., Delwiche, L., Hansen, R. L., Ozonoff, S., Ma, C. C., McCanlies, E. C., Bennett, D. H., Hertz-Picciotto, I., Tancredi, D. J., & Volk, H. E. (2017). Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorder. Environmental Health Perspectives, 125, 097007. https://doi.org/10.1289/ehp604
Shelton, J. F., Geraghty, E. M., Tancredi, D. J., Delwiche, L. D., Schmidt, R. J., Ritz, B., Hansen, R. L., & Hertz-Picciotto, I. (2014). Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environmental Health Perspectives, 122, 1103–1109. https://doi.org/10.1289/ehp.1307044
Stroup, D. F., Berlin, J. A., Morton, S. C., Olkin, I., Williamson, G. D., Rennie, D., Moher, D., Becker, B. J., Sipe, T. A., & Thacker, S. B. (2000). Meta-analysis of observational studies in epidemiology: A proposal for reporting. JAMA, 283, 2008–2012. https://doi.org/10.1001/jama.283.15.2008
Topal, A., Alak, G., Ozkaraca, M., Yeltekin, A. C., Comaklı, S., Acıl, G., Kokturk, M., & Atamanalp, M. (2017). Neurotoxic responses in brain tissues of rainbow trout exposed to imidacloprid pesticide: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and acetylcholinesterase activity. Chemosphere, 175, 186–191. https://doi.org/10.1016/j.chemosphere.2017.02.047
Viel, J.-F., Rouget, F., Warembourg, C., Monfort, C., Limon, G., Cordier, S., & Chevrier, C. (2017). Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: The PELAGIE mother-child cohort. Occupational and Environmental Medicine, 74, 275–281. https://doi.org/10.1136/oemed-2016-104035
von Ehrenstein, O. S., Ling, C., Cui, X., Cockburn, M., Park, A. S., Yu, F., Wu, J., & Ritz, B. (2019). Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: Population based case-control study. BMJ, 364, l962. https://doi.org/10.1136/bmj.l962
Wang, Y., Tang, S., Xu, S., Weng, S., & Liu, Z. (2016). Maternal body mass index and risk of autism spectrum disorders in offspring: A meta-analysis. Scientific Reports, 6, 34248. https://doi.org/10.1038/srep34248
Wells, G. A., O’Connell, B. S. D., Peterson, J., Welch, V., Losos, M., & Tugwell, P. (2011). The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. The Ottawa Health Research Institute.
Xu, G., Jing, J., Bowers, K., Liu, B., & Bao, W. (2014). Maternal diabetes and the risk of autism spectrum disorders in the offspring: A systematic review and meta-analysis. Journal of Autism and Developmental Disorders, 44, 766–775. https://doi.org/10.1007/s10803-013-1928-2
Zhu, Z., Tang, S., Deng, X., & Wang, Y. (2020). Maternal systemic lupus erythematosus, rheumatoid arthritis, and risk for autism spectrum disorders in offspring: A meta-analysis. Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s10803-020-04400-y
Author information
Authors and Affiliations
Contributions
YW conceived of the study, participated in its design and coordination and drafted the manuscript; ST participated in the design and interpretation of the data; SW participated in the design and coordination of the study and performed the measurement; LW, LY participated in the design of the study and performed the statistical analysis; LW, DS conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Research Involving Human and Animal Participants
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Wang, L., Tang, S., Wu, S. et al. Maternal Exposure to Pesticides and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis. J Autism Dev Disord 52, 1640–1651 (2022). https://doi.org/10.1007/s10803-021-05063-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10803-021-05063-z