Phthalates and bisphenols early-life exposure, and childhood allergic conditions: a pooled analysis of cohort studies

Thomas Boissiere-O'Neill; Nina Lazarevic; Peter D Sly; Anne-Louise Ponsonby; Aimin Chen; Meghan B Azad; Joseph M Braun; Jeffrey R Brook; David Burgner; Bruce P Lanphear; Theo J Moraes; Richard Saffery; Padmaja Subbarao; Stuart E Turvey; Kimberly Yolton; CHILD investigator group; BIS investigator group; Dwan Vilcins

doi:10.1038/s41370-025-00790-2

Phthalates and bisphenols early-life exposure, and childhood allergic conditions: a pooled analysis of cohort studies

J Expo Sci Environ Epidemiol. 2025 Jul 3. doi: 10.1038/s41370-025-00790-2. Online ahead of print.

Authors

Thomas Boissiere-O'Neill¹, Nina Lazarevic², Peter D Sly³, Anne-Louise Ponsonby⁴, Aimin Chen⁵, Meghan B Azad⁶, Joseph M Braun⁷, Jeffrey R Brook⁸, David Burgner⁹, Bruce P Lanphear¹⁰, Theo J Moraes¹¹, Richard Saffery⁹, Padmaja Subbarao¹¹, Stuart E Turvey¹², Kimberly Yolton¹³; CHILD investigator group; BIS investigator group; Dwan Vilcins³

Collaborators Collaborators

CHILD investigator group:
Elinor Simons, Piushkumar J Mandhane
BIS investigator group:
Peter Vuillermin, Mimi L K Tang, Fiona Collier, Leonard Harrison, Sarath Ranganathan, Toby Mansell, Martin O'Hely, Lawrence Gray

Affiliations

¹ The University of Queensland, Child Health Research Centre, The Children's Health and Environment Program, Brisbane, QLD, Australia. t.boissiereoneill@uq.edu.au.
² National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT, Australia.
³ The University of Queensland, Child Health Research Centre, The Children's Health and Environment Program, Brisbane, QLD, Australia.
⁴ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
⁵ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Children's Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
⁷ Department of Epidemiology, Brown University, Providence, RI, USA.
⁸ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁹ Murdoch Children's Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, VIC, Australia.
¹⁰ Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
¹¹ Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
¹² Department of Pediatrics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹³ Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.

PMID: 40610791
DOI: 10.1038/s41370-025-00790-2

Abstract

Background: Exposure to plastic additives, such as phthalates and bisphenols, has been associated with a higher risk of allergic conditions, but the evidence is inconsistent for children younger than five.

Objective: To examine the association between pre- and postnatal urinary phthalates and bisphenols, and allergic conditions, and potential effect modification by sex, in pre-school children, through a pooled analysis.

Methods: We pooled data from the Barwon Infant Study (Australia), the Canadian Healthy Infant Longitudinal Development Study (Canada), the Health Outcomes and Measures of the Environment (United States) and the Environmental Influences on Child Health Outcomes-wide cohorts (United States). Urinary phthalates and bisphenols were measured during pregnancy and early childhood. We estimated daily intakes from urinary concentrations, except for mono-(3-carboxypropyl) phthalate (MCPP). Outcomes, including asthma, wheeze, eczema, and rhinitis, were assessed up to five years of age through questionnaires and clinical assessments. We used generalised estimating equations for single compounds and quantile G-computation for the chemical mixtures.

Results: 5306 children were included. A two-fold increase in prenatal dibutyl phthalates (DBP; risk ratio [RR] = 1.08; 95% confidence interval [CI]: 1.00-1.16) and benzyl butyl phthalate (BBzP; RR = 1.06; 95%CI: 1.00-1.12) increased the risk of asthma in children under five. Prenatal MCPP levels were associated with rhinitis (RR = 1.05; 95%CI: 1.01-1.09). Postnatal BBzP levels increased the risk of wheezing (RR = 1.05; 95%CI 1.01-1.09), as well as di(2-ethylhexyl) phthalate (DEHP; RR = 1.06; 95%CI: 1.01-1.11) and MCPP (RR = 1.09; 95%CI: 1.04-1.14). These were also inversely associated with eczema. A one-quartile increase in the postnatal chemical mixture increased the risk of wheezing (RR = 1.14; 95%CI: 1.02-1.26). There was limited evidence of effect modification by sex.

Impact: Phthalates and bisphenols are widespread and may contribute to allergic conditions in children. We pooled data from 5000 children across multiple birth cohorts, suggesting that early-life exposure to these chemicals is associated with increased risks of asthma, wheezing, and rhinitis by age five. We further investigated the timing of exposure, non-linear dose-response relationships, and effect measure modification by sex. This study provides a comprehensive assessment of early-life exposure to phthalates and bisphenols and strengthens the evidence for their role in the development of childhood allergic outcomes.

Keywords: Allergies; Asthma; Bisphenols; Children; Phthalates; Pooled-analysis.