Gestational Exposure to 10 Classes of Priority Chemicals and Birth Outcomes in the ECHO Cohort

Importance: Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. Objective: To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. Design, Setting, and Participants: In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. Exposures: In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). Main Outcomes and Measures: Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. Results: In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56% [2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1-34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95% CI, -1.0 to -0.1 days) younger gestational age (preterm birth OR, 1.16 [95% CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95% CI, -0.11 to -0.02) lower BW-GA z score (SGA OR, 1.09 [95% CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; for example, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95% CI, -0.08 to -0.01) lower BW-GA z score (SGA OR, 1.13 [95% CI, 1.01-1.27]). Conclusions and Relevance: This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lower BW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.

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Journal
JAMA Network Open
Published
2026-06-17
DOI
https://doi.org/10.1001/jamanetworkopen.2026.18883
Primary Topic
Effects and risks of endocrine disrupting chemicals
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article
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article

Gestational Exposure to 10 Classes of Priority Chemicals and Birth Outcomes in the ECHO Cohort

Casper G. Bendixsen, James E. Gern, Diana C. Pacyga, A W Dunlop et al.
JAMA Network Open
Effects and risks of endocrine disrupting chemicals
article

Gestational Exposure to 10 Classes of Priority Chemicals and Birth Outcomes in the ECHO Cohort

Casper G. Bendixsen, James E. Gern, Diana C. Pacyga, A W Dunlop, José F. Cordero, Lisa Croen, Lisa P. Jacobson, John D. Meeker, Akram N. Alshawabkeh, Perera Fp, Traci A. Bekelman, Courtney K. Blackwell, Jane E. Freedman, Xiaoshuang Xun, Shohreh F. Farzan, Jordan R. Kuiper, D. J. Barr, Michelle Macy, Priya Duggal, Daphne Koinis Mitchell, Christina A. Porucznik, D Dabelea, Sean Deoni, Ashley F. Sullivan, Catherine Monk, C Vanesa Padilla Breton, Tenneill Murray, John Meeker, Hans-Georg Mueller, Theresa Bastain, Emily Knapp, Diane Catellier, Megan E. Romano, Courtney Carignan, John A. McLean, Jonathan Posner, Greta Wilkening, Amy Elliott, Amii Kress, Brianna F. Moore, Richard Gershon, Maxwell A. Mansolf, Christian Douglas, C J Karr, R L Miller, M Karagas, Wei Perng, Leonardo Trasande, Emily S. Barrett, Ravi V. Shah, Jiwon Oh, Cristiane S. Duarte, Frank D. Gilliland, P Brian Smith, Qi Zhao, Allison R. Sherris, Yeyi Zhu, Rebecca J. Schmidt, Deborah H. Bennett, Patricia A. Brennan, Carlos A. Camargo, David Cella, Emily Ho, Monique M. Hedderson, Suman R. Das, Deborah J. Watkins, Claudia Lugo-Candelas, Linda Adair, Tracey J. Woodruff, Leonard B. Bacharier, Assiamira Ferrara, Sheryl Magzamen, Zhaozhong Zhu, Jessie P. Buckley, Susan L. Schantz, Viren D'Sa, Simon A. Mallal, John Ainsworth, Rachel Morello-Frosch, Glorisa Canino, Thomas G. O’Connor, Jin-Shei Lai, Anne P. Starling, L Kristin Newby, Sheela Sathyanarayana, Joseph M. Braun, Edo Pellizzari, Zhongmin Li, Julie B. Herbstman, Monica McGrath, Kohei Hasegawa, Heather E. Volk, Kurunthachalam Kannan, Meghan H. Shilts, Deborah J. Rinehart, Christine Hockett
article en

Abstract

Importance: Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. Objective: To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. Design, Setting, and Participants: In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. Exposures: In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). Main Outcomes and Measures: Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. Results: In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56% [2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1-34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95% CI, -1.0 to -0.1 days) younger gestational age (preterm birth OR, 1.16 [95% CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95% CI, -0.11 to -0.02) lower BW-GA z score (SGA OR, 1.09 [95% CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; for example, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95% CI, -0.08 to -0.01) lower BW-GA z score (SGA OR, 1.13 [95% CI, 1.01-1.27]). Conclusions and Relevance: This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lower BW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.

JAMA Network OpenVol. 9(6)
Rutgers, The State University of New Jersey (US), Dartmouth College (US), University of North Carolina at Chapel Hill (US), University of Southern California (US), New York State Department of Health (US), Milken Institute (US), Wadsworth Center (US), Kaiser Permanente (US), Johns Hopkins University (US), Emory University (US), University of Illinois Urbana-Champaign (US), University of Tennessee Health Science Center (US), Outcomes Research Consortium (US), RTI International (US), University of California, San Francisco (US), George Washington University (US), University of Washington (US), Washington University in St. Louis (US), Cardiovascular Institute of the South (US), Brown University (US), University of Michigan (US), Spencer Foundation (US), Seattle Children's Hospital (US), Environmental and Occupational Health Sciences Institute (US), Wagner College (US), University of Rochester (US), New York University (US), Columbia University (US), University of California, Davis (US), Michigan State University (US), University of California, Berkeley (US), Stanford University (US), Icahn School of Medicine at Mount Sinai (US)
Openalex Percentile: Top 8%
Effects and risks of endocrine disrupting chemicals
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