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Prenatal phthalate mixture exposure increases early childhood internalising problems via maternal oxidative stress
Sarah Thomson1, Katherine Drummond1, Martin O'Hely2
1The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; The University of Melbourne, The Florey Department of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Insights
Prenatal exposure to phthalates, common chemicals, may increase children's internalizing problems. Maternal oxidative stress appears to be a key pathway linking phthalate exposure to these issues in early childhood.
Area of Science:
- Environmental Health
- Developmental Psychology
- Toxicology
Background:
- Prenatal phthalate exposure is linked to childhood internalizing problems.
- Maternal oxidative stress is a potential mediator, but this pathway is understudied.
- Phthalates can induce oxidative stress, which is associated with behavioral issues.
Purpose of the Study:
- Investigate the mixture effect of prenatal phthalate exposure on maternal oxidative stress.
- Assess if maternal oxidative stress mediates the link between phthalate exposure and early internalizing problems.
- Examine the role of phthalates in child behavioral development.
Main Methods:
- Population-based birth cohort study (Barwon Infant Study) of 1,074 children.
- Measured phthalate metabolites and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) in maternal urine.
- Assessed child internalizing problems at ages 2 and 4 years using validated questionnaires.
- Utilized weighted quantile sum regression and Bayesian kernel machine regression for mixture analysis.
- Employed counterfactual mediation analyses to test the mediating role of oxidative stress.
Main Results:
- Higher prenatal phthalate mixture exposure was associated with increased maternal oxidative stress.
- Dimethyl phthalate and diethyl phthalate were identified as major contributors to the phthalate mixture effect.
- Evidence supported oxidative stress as a mediator in the association between prenatal phthalate exposure and internalizing problems.
- Findings were consistent across different statistical models and validation techniques.
Conclusions:
- Maternal oxidative stress is a significant pathway linking prenatal phthalate mixture exposure to early childhood internalizing problems.
- Co-exposure to multiple phthalates during pregnancy poses a heightened risk for child behavioral development.
- Interventions focusing on reducing maternal oxidative stress may help mitigate harm from phthalate exposure.
- Findings support enhanced chemical regulation and maternal health monitoring during pregnancy.
Abstract:
Prenatal phthalate exposure has been linked to internalising problems in children. Maternal oxidative stress is a plausible biological mechanism underlying this association as it is induced by phthalates and is associated with early internalising problems, but this pathway has not yet been empirically tested. In the Barwon Infant Study, a population-based birth cohort of 1,074 Australian children, we investigated the potential mixture effect of prenatal phthalate exposure on maternal oxidative stress and assessed whether oxidative stress mediates the relationship between the prenatal phthalate mixture and early internalising problems. Concentrations of phthalate metabolites and nucleic acid oxidation biomarkers (8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine) were measured in third-trimester maternal urine, and phthalate daily intakes estimated. Internalising problems were assessed at ages 2 and 4 years using the parent-report Child Behavior Checklist and Strengths and Difficulties Questionnaire, respectively. Applying weighted quantile sum regression with repeated holdout validation, we found that higher phthalate mixture exposure was associated with increased maternal oxidative stress (0.22 standard deviations per interquartile range increase in mixture, 95% CI: 0.13, 0.31), with dimethyl phthalate and diethyl phthalate as the top contributors. Bayesian kernel machine regression yielded comparable results. For all child outcomes, counterfactual mediation analyses across holdout datasets revealed evidence of mediating effects, suggesting that oxidative stress is a pathway through which prenatal phthalate mixture exposure increases early-childhood internalising problems. These findings highlight the heightened risk associated with co-exposure to multiple phthalates during pregnancy and the potential to mitigate this harm not only through improved chemical regulation but also by monitoring and reducing maternal oxidative stress.
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