First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy

Sabrina M Bedell^{1

2}, Grace R Lyden³, Sheela Sathyanarayana^{4

5}, Emily S Barrett⁶, Kelly K Ferguson⁷, Ashley Santilli⁸, Nicole R Bush⁹, Shanna H Swan¹⁰, Thomas F McElrath¹¹, Ruby H N Nguyen¹²

Affiliations

¹ Department of Women's Health, Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN 55454, USA.
² Division of Gynecologic Oncology, Women's Health Institute, Cleveland Clinic Foundation, Cleveland, OH 44106, USA.
³ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.
⁴ Department of Pediatrics, Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98145, USA.
⁵ Seattle Children's Research Institute, Seattle, WA 98121, USA.
⁶ Department of Biostatistics and Epidemiology, Rutgers School of Public Health and Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.
⁷ Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
⁸ Department of Neurology, Mayo Clinic, Rochester, MN 55904, USA.
⁹ Departments of Psychiatry and Behavioral Sciences and of Pediatrics, University of California at San Francisco, San Francisco, CA 94143, USA.
¹⁰ Department of Preventive Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹² Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.

PMID: 34682373
PMCID: PMC8536149
DOI: 10.3390/ijerph182010627

First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy

Sabrina M Bedell et al. Int J Environ Res Public Health. 2021.

. 2021 Oct 11;18(20):10627.

doi: 10.3390/ijerph182010627.

Authors

Affiliations

¹ Department of Women's Health, Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN 55454, USA.
² Division of Gynecologic Oncology, Women's Health Institute, Cleveland Clinic Foundation, Cleveland, OH 44106, USA.
³ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.
⁴ Department of Pediatrics, Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98145, USA.
⁵ Seattle Children's Research Institute, Seattle, WA 98121, USA.
⁶ Department of Biostatistics and Epidemiology, Rutgers School of Public Health and Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.
⁷ Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
⁸ Department of Neurology, Mayo Clinic, Rochester, MN 55904, USA.
⁹ Departments of Psychiatry and Behavioral Sciences and of Pediatrics, University of California at San Francisco, San Francisco, CA 94143, USA.
¹⁰ Department of Preventive Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹² Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.

PMID: 34682373
PMCID: PMC8536149
DOI: 10.3390/ijerph182010627

Abstract

The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010-2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) were significantly associated with a medical chart diagnosis of PIH. First-trimester mono-n-butyl phthalate (MBP) and MEP along with the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) were each associated with increased systolic blood pressure across pregnancy. In conclusion, several phthalate metabolite concentrations were significantly associated with PIH and greater increases in systolic blood pressure across pregnancy.

Keywords: blood pressure; hypertension; phthalates; preeclampsia; pregnancy.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

**Figure 1**
Hypothesized causal DAG for analysis of phthalate level and PIH. Double-headed arrows indicate a latent confounder.

See this image and copyright information in PMC

References

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First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy

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First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy

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Conflict of interest statement

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