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Urinary phthalate metabolites in pregnant women: occurrences, related factors, and association with maternal hormones

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Abstract 

In this study, we aimed to evaluate phthalate metabolite levels in pregnant women, to explore the factors influencing exposure, and to assess phthalate metabolite levels in relation to thyroid hormone synthesis. We recruited 463 pregnant women and collected urine, blood, and questionnaire data at participant’s first prenatal examination. Ten phthalate metabolites were analyzed: mono-isobutyl phthalate (MiBP); mono-methyl phthalate (MMP); mono-ethyl phthalate (MEP); mono-n-butyl phthalate (MnBP); mono-n-octyl phthalate (MOP); mono-benzyl phthalate (MBzP); and the metabolite of di-2-ethylhexyl phthalate (DEHP), which were mono (2-ethylhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate. Multivariable generalized estimating equation models and linear mixed models were used to predict urinary biomarker concentrations and to assess the associations between phthalate exposure and thyroid hormones. Positive associations were found between phthalate metabolites and lower education (MEP and MOP), living near the road (MEP, MnBP, and ∑DEHP), and consuming more puffed food (MEP and MBzP). In addition, MnBP (percent change [%△] = 4.25; 95% confidence interval [CI] = 0.32, 8.18) and ∑DEHP (%△ = 5.12; 95% CI = 1.25, 8.99) were positively associated with thyroid-stimulating hormones, although MEP and MnBP were inversely associated with free thyroxine and total triiodothyronine. Our findings suggest that certain habits and behaviors were predictive of the positive presence of phthalate metabolites and that certain phthalate esters are associated with altered thyroid hormone levels.

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Data Availability

All data generated or analysed during this study are included in this published article.

Abbreviations

PAEs:

Phthalate esters

mPAEs:

Mono-phthalate metabolite

DMP:

Dimethyl phthalate

DEP:

Di-ethyl-phthalate

DBP:

Di-n-butyl phthalate

DnOP:

Di-n-octyl-phthalate

BBzP:

Butyl benzyl phthalate

DEHP:

Di(2-ethylhexyl)phthalate

∑DEHP:

The sum of metabolite of DEPH

MMP:

Monomethyl phthalate

MEP:

Monoethyl phthalate

MnBP:

Mono-n-butyl phthalate

MiBP:

Mono-isobutyl phthalate

MOP:

Mono-iso-butyl phthalate

MBzP:

Monobenzyl phthalate

MEHP:

Mono (2-ethylhexyl) phthalate

MEHHP:

2-Ethyl-5-hydroxy-hexyl-phthalate

MEOHP:

2-Ethyl-5-oxyhexyl phthalate

MECPP:

Mono-(2-ethyl-5-carboxypentyl) phthalate

FT3 :

Free triiodothyronine

TT3 :

Total triiodothyronine

TT4 :

Total thyroxine

FT4 :

Free thyroxine

TSH:

Thyroid-stimulating hormone

TG:

Thyroglobulin

HPLC–MS:

High-performance liquid chromatography and mass spectrometry

RSD:

Relative standard deviation

CVs:

Coefficients of variation

LOD:

Limit of detection

ANOVA:

Analysis of variance

CI:

Confidence interval

SD:

Standard deviation

IQR:

Interquartile range

EPA:

Environmental Protection Agency

HPT:

Hypothalamic-pituitary-thyroid

SG:

Specific gravity

GEE:

Generalized estimating equation

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Acknowledgements

We are grateful to all participants and collaborators for their contribution to the cohort study.

Funding

This work was supported by the Youth Program of the National Natural Science Foundation of China (21806032).

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Authors and Affiliations

  1. School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China

    Wei Wu, Zhi-li Ma, Fang Yang, Ping Wu, De-xin Zhang, Rong Zeng, Dan-ling Sun & Liu Cao

  2. Ezhou Maternal and Child Health Hospital, Ezhou, 436000, China

    Liu Cao

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  1. Wei Wu
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  2. Zhi-li Ma
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Contributions

Wei Wu: Editing and supervision.

Zhi-li Ma: Original draft preparation.

Fang Yang: Investigation.

Ping Wu: Provision of study materials.

De-xin Zhang: Software.

Rong Zeng: Methodology.

Dan-ling Sun: Visualization.

Liu Cao: Reviewing.

All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Wu or Liu Cao.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Hubei University of Chinese Medicine (No. 2018-IEC-010). Written informed consent was obtained from individual or guardian participants.

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Competing interests

The authors declare no competing interests.

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Responsible Editor: Lotfi Aleya

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Wu, W., Ma, Zl., Yang, F. et al. Urinary phthalate metabolites in pregnant women: occurrences, related factors, and association with maternal hormones. Environ Sci Pollut Res 29, 33372–33382 (2022). https://doi.org/10.1007/s11356-022-18590-8

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