Prenatal Exposure to Phthalates and Neurodevelopment in the CHAMACOS Cohort

Hyland, Carly; Mora, Ana M.; Kogut, Katherine; Calafat, Antònia M.; Harley, Kim G.; Deardorff, Julianna; Holland, Nina; Eskenazi, Brenda; Sagiv, Sharon K.

doi:10.1289/ehp5165

Cited by 58 publications

(34 citation statements)

References 63 publications

(94 reference statements)

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“…Concentrations measured in pregnant women from Korea, China, Taiwan, and the United States were, in general, somewhat higher ( Factor-Litvak et al. 2014 ; Hyland et al. 2019 ; JI Kim et al.…”

Section: Discussionmentioning

confidence: 97%

“…2013 ; Whyatt et al. 2012 ) and IQ ( Hyland et al. 2019 ), but the findings are inconsistent regarding the exact phthalate metabolites, timing of exposure, and the sex-specific effect of the associations.…”

Section: Discussionmentioning

confidence: 99%

“…2012 ). Another study found the averaged sum of high-molecular weight phthalates (HMWPs) and DEHP exposure across pregnancy to be inversely associated with IQ, but only in boys ( Hyland et al. 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

Dries

Guxens

Spaan³

et al. 2020

Environ Health Perspect

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Background: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. Objective: We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. Method: The study sample consisted of 1,282 mother–child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002–2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at , 18–25, and of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test–Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy. Results: Higher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular (95% CI: , )]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di- n -octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex. Conclusions: We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

Dries

Guxens

Spaan³

et al. 2020

Environ Health Perspect

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“…Earlier studies have reported that increased levels of glycerophospholipids were related to liver injury 61 and dementia 62,63 . A previous study reported that exposure to phthalate mixtures or metabolites of phthalates induced abnormal cognitive ability in adult rats 64,65 . So, the increase of glycerophospholipids may be responsible for decreased cognitive flexibility.…”

Section: Discussionmentioning

confidence: 98%

Combining metabolomics with bioanalysis methods to investigate the potential toxicity of dihexyl phthalate

Song

Holck

et al. 2020

Environmental Toxicology

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Dihexyl phthalate (DHP) is one of the most commonly used phthalate esters in various plastic and consumer products. Human are inevitably exposed to DHPs. Although several animal and human experiments have revealed that DHP can cause multiple toxicities, few studies have previously assessed the effects of DHP exposure by liquid chromatography mass spectrometry (LC‐MS) analysis combine with molecular biology methods on human cells. Therefore, the purpose of our study was to investigate the effect of DHP on human cell metabolism by systems biology methods. In this study, U2OS cancer cells were treated with 10 μM DHP for metabolomics analysis and apoptosis analysis at indicate time. Metabolomic study of the metabolic changes caused by DHP in U2OS cells was performed for the first time using integrative liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (LC‐Q‐TOF‐MS). To investigate the possible reason of fatty acids level altered by DHP, we measured some key fatty acid synthesis and oxidation‐related enzyme expression levels by quantitative real‐time PCR (Q‐PCR). Apoptotic cells were analyzed by flow cytometry and apoptosis‐related gene expressions were measured by Q‐PCR. 2′,7′‐Dichlorofluorescein diacetate (DCFH‐DA) staining was used to evaluate ROS content. Partial least squares‐discriminate analysis (PLS‐DA) clearly showed that significant differences in metabolic profiles were observed in U2OS cells exposed to DHP compared with controls. A total of 58 putative metabolites in electrospray ionization source (ESI) + mode and 32 putative metabolites in ESI‐mode were detected, the majority of the differential metabolites being lipids and lipid‐like molecules. Among them, the altered fatty acids level corresponded to expression levels of genes encoding enzymes related to fatty acids synthesis and oxidation. Moreover, DHP induced reactive oxygen species (ROS) accumulation, promoted cell apoptosis and inflammation, and resulted in a significant increase in apoptosis and inflammation‐related gene expression levels compared with controls. In summary, our results suggested that metabolomics combined with molecular bioanalysis methods could be an efficient tool to assess toxic effects, which contribute to explore the possible cytotoxicity mechanisms of DHP, and provide a basis for further research.

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“…Behavior impairments are particularly more prevalent in boys (Q. Zhang et al, 2019). Furthermore, Hyland and colleagues conducted a cohort study in which they evaluated the relationship between maternal urinary phthalate metabolite concentrations and neurodevelopmental outcomes in subjects from age 7 through 16 (Hyland et al, 2019). Despite the fact that most phthalate metabolites showed no association with neurobehavioral patterns, an interesting result is that metabolites of low‐molecular weight phthalates (LMWP) were moderately associated with internalizing and externalizing behaviors in adolescents (Hyland et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The detrimental effect of microplastics on critical periods of development in the neuroendocrine system

Solleiro‐Villavicencio

León

Río-Araiza

et al. 2020

Birth Defects Research

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As a result of human socioeconomic activity, industrial wastes have increased alarmingly. Plastic pollution is globally distributed across the world due to its properties of buoyancy and durability. Two broad classes of plastic-related chemicals are of critical concern for human health-bisphenol-A or BPA, and additives used in the synthesis of plastics, which are known as phthalates. Our exposure to them is ubiquitous because they are used in the production of materials that we use daily such as polycarbonate plastics, epoxy resins, flooring, automotive parts, medical devices, dental sealants, and children's toys. Since these compounds are not covalently bound to the products, they easily leach from them, leading to high human exposure. Both, BPA and phthalates, are endocrine-disruptor compounds (EDCs) with steroidogenic activity, and can bind to different receptors, such as estrogen, androgen, PPAR-γ, and AhR. These pathways are part of the complex regulatory neuroendocrine network, since its cellular components not only express neuroendocrine receptors, but synthesize and respond to several hormones and other endocrine ligands. On the other hand, the effects of BPA and phthalates on neuroendocrine diseases have been poorly studied and the available data are inconclusive. This can be attributed to the enormous variety of animal models and the different doses used in experiments or levels found in humans. However, what is clear is that exposure to both EDCs during critical life stages induces many changes in the neuroendocrine system of exposed humans that are correlated with different reproductive and neurological diseases.

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Prenatal Exposure to Phthalates and Neurodevelopment in the CHAMACOS Cohort

Cited by 58 publications

References 63 publications

Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

Combining metabolomics with bioanalysis methods to investigate the potential toxicity of dihexyl phthalate

The detrimental effect of microplastics on critical periods of development in the neuroendocrine system

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