Prenatal Organophosphate Exposure and Autism-Related Traits in Children

Importance Organophosphate pesticides (OPs) are established neurotoxicants; prenatal OP exposure is widespread in the US population, primarily through diet. Evidence linking prenatal OP exposure to autism spectrum disorder (ASD) and autism-related traits remains inconsistent. Objective To examine the association between prenatal OP exposure and autism-related traits in childhood and to assess potential differences in the association by child sex and maternal diet. Design, Setting, and Participants This pooled prospective cohort study used harmonized data from mother-child pairs from 20 study sites in the Environmental influences on Child Health Outcomes (ECHO) cohort. Participants were recruited from January 1997 through December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 and November 2025. Exposure Prenatal OP exposure using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy) and the sum of 6 dialkyl phosphate (ΣDAP) metabolites. Main Outcomes and Measures Parents reported autism-related traits in children using the Social Responsiveness Scale (SRS). Multivariable linear, quantile, and logistic regression models were used to estimate associations between biomarkers and SRS T scores overall and by child sex, adjusting for maternal sociodemographic and behavioral factors. We further adjusted for dietary factors in additional models and tested effect modification by maternal diet quality in exploratory analyses. Results Among 3339 mother-child pairs examined, mean (SD) maternal age was 31 (6) years, 1665 children (49.9%) were female, and the SRS was administered at a mean (SD) age of 6.4 (3.87) years. Crude or minimally adjusted models suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores, but these associations attenuated and lost statistical significance after full adjustment (β per doubling of TCPy concentration [ng/mL] = −0.13; 95% CI, −0.57 to 0.31; β per doubling of ΣDAP [nmol/L] = −0.42; 95% CI, −1.03 to 0.19). Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by diet quality. Conclusions and Relevance In this large, prospective cohort study among the ECHO cohort, prenatal OP exposure was not associated with autism-related traits in childhood. Given the known adverse impacts of pesticides in other contexts, further research should consider interactions with other factors, genetic susceptibility, higher exposures, or combined chemical mixtures.

Authors

Institutions

Publication Details

Journal
Archives of Pediatrics and Adolescent Medicine
Published
2026-08-24
DOI
https://doi.org/10.1001/jamapediatrics.2026.3785
Primary Topic
Pesticide Exposure and Toxicity
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Prenatal Organophosphate Exposure and Autism-Related Traits in Children

Apollo Kivumbi, Casper G. Bendixsen, Mengling Liu, Diane R. Gold et al.
Archives of Pediatrics and Adolescent Medicine
Pesticide Exposure and Toxicity
article

Prenatal Organophosphate Exposure and Autism-Related Traits in Children

Apollo Kivumbi, Casper G. Bendixsen, Mengling Liu, Diane R. Gold, James E. Gern, Haleigh Cavalier, C A Camargo, Daniel J. Jackson, Suman Das, Jennifer Ames, Gurjit K. Khurana Hershey, Tina V. Hartert, José F. Cordero, Lisa Croen, Anne P. Starling, Meghan H. Shilts, Lisa P. Jacobson, Akram N. Alshawabkeh, Carrie V. Breton, Monica McGrath, Susan V. Lynch, Amii Kress, Traci A. Bekelman, Christine L.M. Joseph, Emily Ho, Akhgar Ghassabian, Courtney K. Blackwell, Meyer Kattan, Kurunthachalam Kannan, Jane E. Freedman, George T. O’Connor, Amanda V. Bakian, Michelle Macy, Jin‐Shei Lai, Deborah H. Bennett, Priya Duggal, Patricia A. Brennan, Daphne Koinis Mitchell, Zhaozhong Zhu, Yelena Afanasyeva, Heather E. Volk, Sean Deoni, Yuyan Wang, Ashley F. Sullivan, Catherine Monk, Dana Dabelea, Tenneill Murray, Robert F. Lemanske, John Meeker, Hans-Georg Mueller, Viren D'Sa, Carole Ober, Linda Adair, Deborah J. Rinehart, Julie B. Herbstman, Claudia Lugo-Candelas, John Ainsworth, Christine Hockett, Leonard B. Bacharier, Monique M. Hedderson, Ravi V. Shah, Christine C. Johnson, Sheryl Magzamen, Margaret R. Karagas, Emily Knapp, Theresa M. Bastain, Stephanie M. Eick, Greta Wilkening, Amy Elliott, Brianna F. Moore, Maxwell A. Mansolf, Glorisa Canino, Zhongmin Li, Wei Perng, Assiamira Ferrara, Diane Catellier, Simon A. Mallal, Anne L. Dunlop, Christian Douglas, Jonathan Posner, Richard Gershon, John A. McLean, Dennis Ownby, Leonardo Trasande, Yu Chen, David Cella, Kristen Lyall, Allison R. Sherris, Kohei Hasegawa, L Kristin Newby, Cristiane S. Duarte, Rachel L. Miller, Rebecca J. Schmidt, P Brian Smith, Jaclyn M. Goodrich, Susan L. Schantz, Thomas G. O’Connor, Nicole B. Alkhouri
article en

Abstract

Importance Organophosphate pesticides (OPs) are established neurotoxicants; prenatal OP exposure is widespread in the US population, primarily through diet. Evidence linking prenatal OP exposure to autism spectrum disorder (ASD) and autism-related traits remains inconsistent. Objective To examine the association between prenatal OP exposure and autism-related traits in childhood and to assess potential differences in the association by child sex and maternal diet. Design, Setting, and Participants This pooled prospective cohort study used harmonized data from mother-child pairs from 20 study sites in the Environmental influences on Child Health Outcomes (ECHO) cohort. Participants were recruited from January 1997 through December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 and November 2025. Exposure Prenatal OP exposure using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy) and the sum of 6 dialkyl phosphate (ΣDAP) metabolites. Main Outcomes and Measures Parents reported autism-related traits in children using the Social Responsiveness Scale (SRS). Multivariable linear, quantile, and logistic regression models were used to estimate associations between biomarkers and SRS T scores overall and by child sex, adjusting for maternal sociodemographic and behavioral factors. We further adjusted for dietary factors in additional models and tested effect modification by maternal diet quality in exploratory analyses. Results Among 3339 mother-child pairs examined, mean (SD) maternal age was 31 (6) years, 1665 children (49.9%) were female, and the SRS was administered at a mean (SD) age of 6.4 (3.87) years. Crude or minimally adjusted models suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores, but these associations attenuated and lost statistical significance after full adjustment (β per doubling of TCPy concentration [ng/mL] = −0.13; 95% CI, −0.57 to 0.31; β per doubling of ΣDAP [nmol/L] = −0.42; 95% CI, −1.03 to 0.19). Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by diet quality. Conclusions and Relevance In this large, prospective cohort study among the ECHO cohort, prenatal OP exposure was not associated with autism-related traits in childhood. Given the known adverse impacts of pesticides in other contexts, further research should consider interactions with other factors, genetic susceptibility, higher exposures, or combined chemical mixtures.

Archives of Pediatrics and Adolescent Medicine
Dartmouth College (US), University of Southern California (US), New York State Department of Health (US), Wadsworth Center (US), Kaiser Permanente (US), Johns Hopkins University (US), Emory University (US), University of Illinois Urbana-Champaign (US), University of Washington (US), University of Utah (US), University of Michigan (US), Huntsman Cancer Institute (US), NYU Langone Health (US), Cohort (United Kingdom) (GB), Wagner College (US), University of Rochester (US), Drexel University (US), Columbia University (US), University of California, Davis (US), Michigan State University (US)
Openalex Percentile: Top 11%
Pesticide Exposure and Toxicity
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.