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Maternal Exposure to Per- and Polyfluoroalkyl Substances: Implications for Intrahepatic Cholestasis of Pregnancy and Adverse Birth Outcomes

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Abstract

Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been linked to maternal complications and exerts a long-term impact on fetal growth. However, information regarding the effects of PFAS on intrahepatic cholestasis of pregnancy (ICP) with hepatic biomarkers underlying the association is nascent. By analyzing 15 PFAS compounds in maternal serum from 78 women with a diagnosis of ICP and 164 healthy participants, this study provided epidemiological associations between PFAS exposure and ICP risks, liver function, and their potential influence on birth outcomes. As a result, the main contributors were perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which accounted for 21% and 23% of the total PFAS exposure, respectively. Results revealed that each logarithmic increase in serum PFOA was associated with nearly tripled risk of ICP during pregnancy. In contrast, perfluorohexanesulfonic acid (PFHxS), 4:2 fluorotelomer sulfonate (4:2 FTS), and 3H-perfluoro-3-[(3-methoxy-propoxy) propanoic acid] (ADONA) showed negative associations on liver toxicity. In addition, increased estradiol and estriol levels in the serum were observed significantly associated with higher exposure of PFOA, perfluorodecanoic acid (PFDA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA). Concerning the birth outcomes, increased risks for small-for-gestational-age and intrauterine development were found for the higher PFOA, PFOS, and 6:2-Cl-PFESA exposure. Notably, higher levels of PFOA exposure may be linked to an increased risk of intrauterine hypoxia due to impaired transfer of oxygen across the placenta. These findings provide valuable insights for environmental and public health considerations, highlighting the importance of considering maternal PFAS exposure to ICP and birth outcomes.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Dr. Y Tian acknowledges support from the National Key R&D Program of China (Grant No. 2018YFC1004302). Dr. C Xu acknowledges the support from the National Natural Science Foundation of China (Grant No. 22006010). Dr. S Yin acknowledges the support from FWO junior postdoctoral fellowships (1270521N), Basic Scientific Research Special Funds of Zhejiang Shuren University (2021XZ017), and National Natural Science Foundation of China (22276166). We thank Prof. Dr. Adrian Covaci for his help in preparing this manuscript. We sincerely thank the medical and clinical staff at the Women’s Hospital, School of Medicine, Zhejiang University for their hard work, and would like to thank the mothers and infants who volunteered to participate in this study.

Funding

Dr. Y Tian acknowledges support from the National Key R&D Program of China (Grant No. 2018YFC1004302). Dr. C Xu acknowledges the support from the National Natural Science Foundation of China (Grant No. 22006010). Dr. S Yin acknowledges the support from FWO junior postdoctoral fellowships (1270521N), Basic Scientific Research Special Funds of Zhejiang Shuren University (2021XZ017), and National Natural Science Foundation of China (22276166).

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Authors and Affiliations

  1. Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China

    Yonghong Tian & Long Zhang

  2. College of Environmental Science and Engineering, Donghua University, Shanghai, 201620, China

    Chenye Xu

  3. Department of Infection Control, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Dake Shi

  4. Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium

    Francesca Cappelli & Shanshan Yin

  5. Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy (IRA), Zhejiang Shuren University, Hangzhou, 310015, China

    Shanshan Yin

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  2. Chenye Xu
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  3. Long Zhang
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  4. Dake Shi
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  5. Francesca Cappelli
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  6. Shanshan Yin
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Contributions

YT contributed toward conceptualization, resources, investigation, data curation, writing—original draft, writing—review & editing, and funding acquisition. CX contributed toward conceptualization, formal analysis, writing—original draft, writing—review & editing, project administration, and funding acquisition. LZ contributed toward sample collection and investigation. DS contributed toward writing—original draft. FC contributed toward writing—original draft, and writing—review & editing; SY contributed toward conceptualization, formal analysis, writing—original draft, writing—review & editing, visualization, and funding acquisition.

Corresponding author

Correspondence to Shanshan Yin.

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Ethical Approval

The protocols of this work were approved by the Medical Ethics Committees of Women’s Hospital, School of Medicine, Zhejiang University (IRB-20200055-R). All these participants signed the written informed consent after being briefed on the study’s purpose.

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Tian, Y., Xu, C., Zhang, L. et al. Maternal Exposure to Per- and Polyfluoroalkyl Substances: Implications for Intrahepatic Cholestasis of Pregnancy and Adverse Birth Outcomes. Expo Health (2024). https://doi.org/10.1007/s12403-023-00620-6

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