Abstract
Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32–5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82–7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10–4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80 µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.
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Data availability
Data associated with the present study can be accessed on request to the author (xxlwangxia@163.com).
Abbreviations
- PAEs:
-
Phthalates
- ZBC:
-
Zunyi Birth Cohort
- MMP:
-
Mono-methyl
- MEP:
-
Mono-methyl phthalate
- MiBP:
-
Mono-ethyl phthalate
- MBP:
-
Mono-butyl phthalate
- MOP:
-
Mono-octyl phthalate
- MBzP:
-
Mono-benzyl phthalate
- MEHP:
-
Mono(2-ethylhexyl) phthalate
- MEOHP:
-
Mono(2-ethyl-5-oxohexyl) phthalate
- MEHHP:
-
Mono(2-ethyl-5-hydroxyhexyl) phthalate
- OR :
-
Odds ratio
- CI :
-
Confidence interval
- EVT:
-
Extravillous trophoblast
- BMI:
-
Body mass index
- GC–MS/MS:
-
High-performance gas chromatography–mass spectrometry
- LOD:
-
The limit of detection
- Cr:
-
Creation
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Acknowledgements
The authors thank all the participants and investigators and the National Key R&D Program of China, Science & Technology Program of Guizhou Province and The Guizhou Province Foundation for postgraduate Scientific Research Found Project for funding.
Funding
This work was supported by the National Key R&D Program of China (2018YFC1004300, 2018YFC1004302), the Science & Technology Program of Guizhou Province, China (QKHHBZ [2020]3002) and The Guizhou Province Foundation for Postgraduate Scientific Research Found Project YJSCXJH [2020] 167 and the Guizhou Genetic Foundation—ZK [2022] 614.
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Xia Wang: formal analysis, investigation, validation, data curation, writing—original draft, funding acquisition. Caidie He: investigation, data curation, visualization. Nian Wu: data curation, conceptualization. Yingkuan Tian: methodology, validation. Shimin Xiong: data curation, validation. Yijun Liu: data curation, validation. Yan Xie: data curation, validation. Kunming Tian: data curation, validation. Linglu Wang: investigation, validation. Juan Liao: investigation, validation. Derong Fang: investigation, validation. Songlin An: investigation, conceptualization. Wei Chen: investigation, conceptualization. Xiang Liu: investigation, conceptualization. Hongyu Yuan: investigation, data curation. Jingyi Huang: investigation, conceptualization. Xiaoshan Chen: investigation, conceptualization. Li Zhang: investigation, data curation. Quan Li: project administration, investigation, validation, resources. Xubo Shen: project administration, investigation, validation, resources. Yuanzhong Zhou: funding acquisition, investigation, validation, resources, writing–review and editing, funding acquisition.
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Wang, X., He, C., Wu, N. et al. Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case–control study of the Zunyi Birth Cohort. Environ Sci Pollut Res 30, 23124–23134 (2023). https://doi.org/10.1007/s11356-022-23717-y
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DOI: https://doi.org/10.1007/s11356-022-23717-y