Prenatal phthalate exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE cohort

Emily S Barrett; Matthew Corsetti; Drew Day; Sally W Thurston; Christine T Loftus; Catherine J Karr; Kurunthachalam Kannan; Kaja Z LeWinn; Alicia K Smith; Roger Smith; Frances A Tylavsky; Nicole R Bush; Sheela Sathyanarayana

doi:10.1016/j.envint.2022.107078

Prenatal phthalate exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE cohort

Environ Int. 2022 Feb:160:107078. doi: 10.1016/j.envint.2022.107078. Epub 2022 Jan 7.

Authors

Affiliations

¹ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: emily.barrett@eohsi.rutgers.edu.
² Department of Biostatistics and Computational Biology, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA.
³ Seattle Children's Research Institute, University of Washington, Seattle, WA 98101, USA.
⁴ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
⁵ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Department of Pediatrics, University of Washington, Seattle, WA 98104, USA.
⁶ Department of Pediatrics and Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.
⁷ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
⁸ Department of Gynecology and Obstetrics, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁹ Hunter Medical Research Institute, University of Newcastle, Newcastle 2300, Australia.
¹⁰ Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
¹¹ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA 94143, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
¹² Seattle Children's Research Institute, University of Washington, Seattle, WA 98101, USA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA; Department of Pediatrics, University of Washington, Seattle, WA 98104, USA.

Abstract

Context: Phthalates may disrupt maternal-fetal-placental endocrine pathways, affecting pregnancy outcomes and child development. Placental corticotropin releasing hormone (pCRH) is critical for healthy pregnancy and child development, but understudied as a target of endocrine disruption.

Objective: To examine phthalate metabolite concentrations (as mixtures and individually) in relation to pCRH.

Design: Secondary data analysis from a prospective cohort study.

Setting: Prenatal clinics in Tennessee, USA.

Patients: 1018 pregnant women (61.4% non-Hispanic Black, 32% non-Hispanic White, 6.6% other) participated in the CANDLE study and provided data. Inclusion criteria included: low-medical-risk singleton pregnancy, age 16-40, and gestational weeks 16-29.

Intervention: None.

Main outcome measures: Plasma pCRH at two visits (mean gestational ages 23.0 and 31.8 weeks) and change in pCRH between visits (ΔpCRH).

Results: In weighted quantile sums (WQS) regression models, phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.07, 95 %CI: 0.02, 0.11) but lower pCRH at Visit 2 (β = -0.08, 95 %CI: -0.14, -0.02). In stratified analyses, among women with gestational diabetes (n = 59), phthalate mixtures were associated with lower pCRH at Visit 1 (β = -0.17, 95 %CI: -0.35, 0.0006) and Visit 2 (β = -0.35, 95 %CI: -0.50, -0.19), as well as greater ΔpCRH (β = 0.16, 95 %CI: 0.07, 0.25). Among women with gestational hypertension (n = 102), phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.20, 95 %CI: 0.03, 0.36) and Visit 2 (β = 0.42; 95 %CI: 0.19, 0.64) and lower ΔpCRH (β = -0.17, 95 %CI: -0.29, -0.06). Significant interactions between individual phthalate metabolites and pregnancy complications were observed.

Conclusions: Phthalates may impact placental CRH secretion, with differing effects across pregnancy. Differences in results between women with and without gestational diabetes and gestational hypertension suggest a need for further research examining whether women with pregnancy complications may be more vulnerable to endocrine-disrupting effects of phthalates.

Keywords: Corticotropin releasing hormone; Endocrine disrupting chemicals; Phthalates; Placenta; Pregnancy complications.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Cohort Studies
Corticotropin-Releasing Hormone*
Female
Humans
Infant
Phthalic Acids* / adverse effects
Placenta
Pregnancy
Pregnancy Outcome
Prospective Studies
Young Adult

Substances

Phthalic Acids
phthalic acid
Corticotropin-Releasing Hormone

Abstract

Publication types

MeSH terms

Substances

Grants and funding