Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program

John D. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: meekerj@umich.edu.
Kristen L. McArthur, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: kmcarth5@jhmi.edu.
Jennifer A. Adibi, Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: adibij@pitt.edu.
Akram N. Alshawabkeh, Northeastern University, Boston, MA, USA. Electronic address: a.alshawabkeh@northeastern.edu.
Emily S. Barrett, Department of Biostatistics and Epidemiology, Rutgers University School of Public Health, Environmental and Occupational Health Institute, Piscataway, NJ, USA. Electronic address: esb104@eohsi.rutgers.edu.
Sara G. Brubaker, Division of Maternal-Fetal Medicine, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: sara.brubaker@nyulangone.org.
Jose F. Cordero, Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens, GA, USA. Electronic address: jcordero@uga.edu.
Dana Dabelea, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: dana.dabelea@cuanschutz.edu.
Anne L. Dunlop, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: amlang@emory.edu.
Julie B. Herbstman, Department of Environmental Health Sciences, Columbia University, New York, NY, USA. Electronic address: jh2678@cumc.columbia.edu.
Linda G. Kahn, Division of Environmental Pediatrics, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: Linda.Kahn@nyulangone.org.
Catherine J. Karr, Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USA. Electronic address: ckarr@uw.edu.
Shilpi Mehta-Lee, Division of Maternal-Fetal Medicine, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: Shilpi.Mehta-Lee@nyulangone.org.
Thomas G. O'Connor, Departments of Psychiatry, Neuroscience and Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA. Electronic address: tom_oconnor@urmc.rochester.edu.
Sheela Sathyanarayana, Department of Pediatrics, Department of Environmental and Occupational Health Sciences, Department of Epidemiology University of Washington and Seattle Children's Research Institute, Seattle, WA, USA. Electronic address: Sheela.sathyanarayana@seattlechildrens.org.
Leonardo Trasande, Department of Pediatrics, New York University, New York, NY, USA. Electronic address: Leonardo.Trasande@nyulangone.org.
Jordan R. Kuiper, Department of Environmental and Occupational Health, The George Washington University, Washington, D.C., USA. Electronic address: jordan.kuiper@gwu.edu.

Document Type

Journal Article

Publication Date

4-20-2024

Journal

Environment international

Volume

187

DOI

10.1016/j.envint.2024.108678

Abstract

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Department

Environmental and Occupational Health

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