Prenatal exposure to phthalates and alternative plasticizers and emotional and behavioral outcomes in early childhood in the Environmental influences on Child Health outcomes (ECHO) cohort

Jiwon Oh; Jessie P Buckley; Sudhi Upadhyaya; Kurunthachalam Kannan; Emily S Barrett; Theresa M Bastain; Carrie V Breton; Stephanie M Eick; Sarah Dee Geiger; Akhgar Ghassabian; Rima Habre; Julie B Herbstman; Deborah Hirtz; Donghai Liang; Kaja LeWinn; John D Meeker; Thomas G O'Connor; Irva Hertz-Picciotto; Douglas Ruden; Sheela Sathyanarayana; Susan L Schantz; Julie B Schweitzer; Anat Sigal; Tracey J Woodruff; Qi Zhao; Rebecca J Schmidt; Deborah H Bennett; ECHO Cohort Consortium

doi:10.1016/j.envint.2025.109647

Prenatal exposure to phthalates and alternative plasticizers and emotional and behavioral outcomes in early childhood in the Environmental influences on Child Health outcomes (ECHO) cohort

Environ Int. 2025 Jun 30:202:109647. doi: 10.1016/j.envint.2025.109647. Online ahead of print.

Authors

Jiwon Oh¹, Jessie P Buckley², Sudhi Upadhyaya³, Kurunthachalam Kannan⁴, Emily S Barrett⁵, Theresa M Bastain⁶, Carrie V Breton⁷, Stephanie M Eick⁸, Sarah Dee Geiger⁹, Akhgar Ghassabian¹⁰, Rima Habre¹¹, Julie B Herbstman¹², Deborah Hirtz¹³, Donghai Liang¹⁴, Kaja LeWinn¹⁵, John D Meeker¹⁶, Thomas G O'Connor¹⁷, Irva Hertz-Picciotto¹⁸, Douglas Ruden¹⁹, Sheela Sathyanarayana²⁰, Susan L Schantz²¹, Julie B Schweitzer²², Anat Sigal²³, Tracey J Woodruff²⁴, Qi Zhao²⁵, Rebecca J Schmidt²⁶, Deborah H Bennett²⁷; ECHO Cohort Consortium

Affiliations

¹ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: jiwoh@ucdavis.edu.
² Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA. Electronic address: Jessie.Buckley@unc.edu.
³ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: supadhy8@jhu.edu.
⁴ Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12237, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA. Electronic address: kurunthachalam.kannan@health.ny.gov.
⁵ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 683 Hoes Ln W, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers, the State University of New Jersey, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA. Electronic address: esb104@eohsi.rutgers.edu.
⁶ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: bastain@usc.edu.
⁷ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: breton@usc.edu.
⁸ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: stephanie.marie.eick@emory.edu.
⁹ Department of Health and Kinesiology, and Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: smurphy7@illinois.edu.
¹⁰ Department of Pediatrics, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA; Department of Population Health, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA. Electronic address: Akhgar.Ghassabian@nyulangone.org.
¹¹ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: habre@usc.edu.
¹² Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY 10032, USA. Electronic address: jh2678@cumc.columbia.edu.
¹³ Department of Neurological Sciences, University of Vermont Medical Center, 111 Colchester Ave, Burlington, VT 05401, USA. Electronic address: deborah.hirtz@uvmhealth.org.
¹⁴ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: donghai.liang@emory.edu.
¹⁵ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, 675 18th Street, San Francisco, CA 94107, USA. Electronic address: kaja.lewinn@ucsf.edu.
¹⁶ Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: meekerj@umich.edu.
¹⁷ Departments of Psychiatry, Neuroscience, Obstetrics and Gynecology, University of Rochester, 500 Joseph C. Wilson Blvd. Rochester, NY 14627, USA. Electronic address: tom_oconnor@urmc.Rochester.edu.
¹⁸ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: iher@ucdavis.edu.
¹⁹ Department of Obstetrics and Gynecology, Wayne State University, 42 W Warren Ave, Detroit, MI 48202, USA. Electronic address: douglasr@wayne.edu.
²⁰ Department of Pediatrics, University of Washington and Seattle Children's Research Institute, 4800 Sand Point Way NE, Seattle, WA 98105, USA. Electronic address: sheela.sathyanarayana@seattlechildrens.org.
²¹ Department of Psychology, and Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: schantz@illinois.edu.
²² UC Davis MIND Institute, 2825 50th St, Sacramento, CA 95817, USA; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California at Davis, 4610 X St, Sacramento, CA 95817, USA. Electronic address: jschweitzer@ucdavis.edu.
²³ Pediatrics, Hackensack University Medical Center, 30 Prospect Ave, Hackensack, NJ 07601, USA. Electronic address: anat.sigal@hmhn.org.
²⁴ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 490 Illinois Street, Floor 10, San Francisco, CA 94143, USA. Electronic address: tracey.woodruff@ucsf.edu.
²⁵ Department of Preventive Medicine, University of Tennessee Health Science Center, 920 Madison Ave, Memphis, TN 38163, USA. Electronic address: qzhao11@uthsc.edu.
²⁶ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: rjschmidt@ucdavis.edu.
²⁷ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: dhbennett@ucdavis.edu.

PMID: 40617232
DOI: 10.1016/j.envint.2025.109647

Abstract

Background: Evidence suggests prenatal phthalate exposure adversely affects children's behavior. However, epidemiological studies on alternative plasticizers remain scarce. This study investigated associations of gestational exposure to phthalates and alternative plasticizers with internalizing and externalizing behaviors in children aged 1.5-5 years.

Methods: The study included 2617 mother-child dyads from 13 Environmental influences on Child Health Outcomes (ECHO) cohorts. Maternal urine samples, primarily collected mid- to late-pregnancy, were analyzed for 27 phthalate metabolites and 6 alternative plasticizer metabolites. Based on detection frequency, metabolite concentrations were modeled either continuously or categorically (Group 1: non-detectable, 2: lower detectable, 3: higher detectable). Covariate-adjusted associations between individual metabolite concentrations and internalizing and externalizing T-scores on the Child Behavior Checklist for Ages 1½-5 were estimated using linear mixed-effects models. Effect modification by child sex was also examined.

Results: An interquartile range increase in mono-benzyl phthalate (MBzP) and membership in Group 3, versus Group 1, for mono-hexyl phthalate (MHxP) were associated with higher externalizing T-scores (β_ext for continuous MBzP = 0.53, 95% CI: 0.05, 1.00; β_ext for MHxP Group 3 = 1.23, 95% CI: 0.35, 2.12). We observed no robust associations between phthalate metabolites and internalizing T-scores, nor between cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl ester (DINCH) metabolites and any behavioral outcomes. Child sex modified associations between several metabolites and externalizing T-scores, although the direction of effect varied by metabolite.

Conclusion: This large-scale study suggests that prenatal exposure to several phthalates, but not to the alternative plasticizer DINCH, may be associated with a small-to-modest increase in externalizing behaviors in young children.

Keywords: Alternative plasticizers; Behaviors; Neurodevelopment; Phthalates; Pregnancy.