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Gestational Exposure to Phthalates and Phthalate Replacements in Relation to Neurodevelopmental Delays in Early
Seonyoung Park1, Emily Zimmerman2, Gredia Huerta-Montañez3
1Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Insights
Gestational exposure to phthalates and their replacements is linked to child neurodevelopmental delays, particularly in boys. These effects impact multiple developmental domains, highlighting the need for further research on these chemicals.
Area of Science:
- Environmental Health
- Developmental Toxicology
- Pediatric Neurodevelopment
Background:
- Phthalates are endocrine-disrupting chemicals with established links to adverse child neurodevelopmental outcomes.
- Inconsistent findings regarding sex-specific effects and limited data on newer phthalate replacement chemicals necessitate further investigation.
- Understanding these associations is crucial for public health, especially concerning vulnerable populations like pregnant women and children.
Purpose of the Study:
- To investigate the association between prenatal exposure to phthalates and phthalate replacement chemicals and child neurodevelopment.
- To examine potential sex-specific differences in these associations across multiple developmental domains.
- To assess neurodevelopmental outcomes at various early childhood time points (6, 12, and 24 months).
Main Methods:
- Analysis of mother-child pairs (N=274) from the PROTECT birth cohort in Puerto Rico.
- Measurement of phthalate metabolites in maternal urine collected during pregnancy.
- Assessment of child neurodevelopment using the Battelle Developmental Inventory-2nd edition (BDI) at 6, 12, and 24 months.
- Application of multivariable linear regression and sex-stratified analyses to examine exposure-outcome associations.
Main Results:
- Prenatal exposure to mono-3-carboxypropyl phthalate (MCPP) was associated with holistic developmental delays across all five BDI domains at 24 months.
- Significant sex-specific effects were observed across all time points, with generally stronger associations in boys.
- Metabolites of di-2-ethylhexyl terephthalate (DEHTP), a phthalate replacement, showed differential associations with adaptive and cognitive domains in boys compared to girls at 6 months.
Conclusions:
- Gestational exposure to phthalates and their replacements is associated with neurodevelopmental delays in children.
- Sex and child age are important factors influencing the impact of these chemical exposures on neurodevelopment.
- Findings underscore the need for continued monitoring and regulation of phthalates and their alternatives due to potential neurodevelopmental risks.
Abstract:
Phthalates have been linked to changes in child neurodevelopment. However, sex-specificity has been reported inconsistently, and little is known about the impact of recent phthalate replacement chemicals. Our analysis included mother−child pairs (N = 274) from the PROTECT birth cohort in Puerto Rico. Phthalate metabolites were measured in multiple maternal urine collected during pregnancy. Neurodevelopment was measured at 6, 12, and 24 months of age using the Battelle Developmental Inventory-2nd edition (BDI), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. Multivariable linear regression was used to examine associations between phthalate metabolite concentrations and BDI scores, adjusting for maternal age, maternal education, child age, and specific gravity. Sex-specificity was assessed with sex X exposure interaction terms and stratified models. Results show that all five domains were significantly associated with mono-3-carboxypropyl phthalate (MCPP) at age 24 months, suggesting a holistic developmental delay related to this metabolite. Sex-specificity existed for all timepoints (p-interaction < 0.2), in general, showing stronger associations among boys. For example, metabolites of a recent phthalate replacement, di-2-ethylhexyl terephthalate (DEHTP), were differentially associated with the adaptive domain (boys −7.53%/IQR, 95% CI: −14.58, −0.48 vs. girls −0.85%/IQR, 95% CI: −5.08, 3.37), and the cognitive domain (boys −6.05%/IQR, 95% CI: −10.88, −1.22 vs. girls −1.93%/IQR, 95%CI: −4.14, 0.28) at 6 months. To conclude, gestational exposure to phthalates and phthalate replacements was associated with neurodevelopmental delay across multiple domains, with differences by sex and child age.
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