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A study on the association of placental and maternal urinary phthalate metabolites

Journal of Exposure Science & Environmental Epidemiology volume 33, pages 264–272 (2023)Cite this article

Abstract

Background

Phthalate exposure in pregnancy is typically estimated using maternal urinary phthalate metabolite levels. Our aim was to evaluate the association of urinary and placental tissue phthalates, and to explore the role of maternal and pregnancy characteristics that may bias estimates.

Methods

Fifty pregnancies were selected from the CANDLE Study, recruited from 2006 to 2011 in Tennessee. Linear models were used to estimate associations of urinary phthalates (2nd, 3rd trimesters) and placental tissue phthalates (birth). Potential confounders and modifiers were evaluated in categories: temporality (time between urine and placenta sample), fetal sex, demographics, social advantage, reproductive history, medication use, nutrition and adiposity. Molar and quantile normalized phthalates were calculated to facilitate comparison of placental and urinary levels.

Results

Metabolites detectable in >80% of both urine and placental samples were MEP, MnBP, MBzP, MECPP, MEOHP, MEHHP, and MEHP. MEP was most abundant in urine (geometric mean [GM] 7.00 ×102 nmol/l) and in placental tissue (GM 2.56 ×104 nmol/l). MEHP was the least abundant in urine (GM 5.32 ×101 nmol/l) and second most abundant in placental tissue (2.04 ×104 nmol/l). In aggregate, MEHP differed the most between urine and placenta (2.21 log units), and MEHHP differed the least (0.07 log units). MECPP was positively associated between urine and placenta (regression coefficient: 0.31 95% CI 0.09, 0.53). Other urine-placenta metabolite associations were modified by measures of social advantage, reproductive history, medication use, and adiposity.

Conclusion

Phthalates were ubiquitous in 50 full-term placental samples, as has already been shown in maternal urine. MEP and MEHP were the most abundant. Measurement and comparison of urinary and placental phthalates can advance knowledge on phthalate toxicity in pregnancy and provide insight into the validity and accuracy of relying on maternal urinary concentrations to estimate placental exposures.

Impact statement

This is the first report of correlations/associations of urinary and placental tissue phthalates in human pregnancy. Epidemiologists have relied exclusively on maternal urinary phthalate metabolite concentrations to assess exposures in pregnant women and risk to their fetuses. Even though it has not yet been confirmed empirically, it is widely assumed that urinary concentrations are strongly and positively correlated with placental and fetal levels. Our data suggest that may not be the case, and these associations may vary by phthalate metabolite and associations may be modified by measures of social advantage, reproductive history, medication use, and adiposity.

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Data availability

Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided. CANDLE is a participating cohort in the National Institutes of Health program Environmental Influences on Child Health Outcomes (ECHO), a mechanism for sharing birth cohort data.

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Acknowledgements

We acknowledge the contributions of the following individuals in the collection of CANDLE data: Phyllis Richey, Maureen Sorrells, Lauren Simms, Matt Hood, Grant Somes, Ron Adkins, Julia Krushkal, Fred Palmer, Fridtjof Thomas, Jeanie Peeples, Priyanka Jani, Laura Murphy, Carolyn Graff, Pamela Connor, Andy Bush, Risa Ramsey, Owen Phillips, Marion Hare, and Anand Kulkarni. We are grateful for the participation of the families enrolled in the CANDLE cohort. We thank Stacey Pharrams of Healthy Start Inc. in reading this manuscript and providing comments.

Funding

This work was supported by the Department of Epidemiology at the University of Pittsburgh, the National Institute of Environmental Health Sciences (NIEHS; grant Nos. 1R01ES029336 and 1R56ES025728–01A1), and the Urban Child Institute.

Author information

Authors and Affiliations

  1. Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Hai-Wei Liang, Xiaoshuang Xun & Jennifer J. Adibi

  2. Center for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

    Nathaniel Snyder

  3. Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Jiebiao Wang & Qing Yin

  4. Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA

    Kaja LeWinn & Nicole R. Bush

  5. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kecia N. Carroll

  6. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Nicole R. Bush

  7. Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, USA

    Kurunthachalam Kannan

  8. Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA

    Emily S. Barrett

  9. MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, Scotland, UK

    Rod T. Mitchell

  10. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    Fran Tylavsky

  11. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA

    Jennifer J. Adibi

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Contributions

HWL carried out the data analysis and helped to write the manuscript. NS developed the method for the analysis of placental tissue phthalates, and helped to write the manuscript. JW contributed the quantile normalization method to compare phthalate levels in the two tissue types, and reviewed the manuscript. XX and QY contributed R code and contributed to the data analysis for this manuscript. KLW, KC, NRB and FT were all part of the original conception of the project, and KLW served as a liaison between the Adibi and CANDLE research groups. KLW, NRB, and KC contributed key perspectives on reporting race differences in these associations. KK analyzed the urinary phthalate metabolites and contributed to the manuscript. EB and RTM offered edits and comments on the manuscript. FT is the original PI of the CANDLE study. JJA conceived of and initiated this research, mentored HWL, XX, and QY, and wrote the manuscript.

Corresponding author

Correspondence to Jennifer J. Adibi.

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The authors declare no competing interests.

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Research was performed in accordance with the Declaration of Helsinki and approved by the Institutional Review Boards at the University of Tennessee Health Science Center and the University of Pittsburgh. The University of Pittsburgh declared this research to be exempt as Pitt investigators had access to de-identified data, and no contact with research participants.

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Liang, HW., Snyder, N., Wang, J. et al. A study on the association of placental and maternal urinary phthalate metabolites. J Expo Sci Environ Epidemiol 33, 264–272 (2023). https://doi.org/10.1038/s41370-022-00478-x

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