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

• Authors: Emily S Barrett, Rutgers Sch Publ Hlth; Matthew Corsetti, University of Rochester; Drew Day, University of Washington; Sally W Thurston, University of Rochester; Christine T Loftus, University of Washington; Catherine J Karr, University of Washington; Kurunthachalam Kannan, New York University; Kaja Z LeWinn, University of California San Francisco; Alicia Smith, Emory University; Roger Smith, University of Newcastle; Frances A Tylavsky, University of Tennessee Health Science Center; Nicole R Bush, University of California San Francisco; Sheela Sathyanarayana, University of Washington
• Journal Title: ENVIRONMENT INTERNATIONAL
• Volume: Volume 160
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD | 2022-01-07, Pages 107078-107078
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.envint.2022.107078
• Subjects: Health Sciences, Epidemiology; Biology, Biostatistics; Health Sciences, Obstetrics and Gynecology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Environmental Sciences; Environmental Sciences & Ecology; Phthalates; Endocrine disrupting chemicals; Pregnancy complications; Corticotropin releasing hormone; Placenta; PREGNANT-WOMEN; METABOLITE CONCENTRATIONS; URINARY CONCENTRATIONS; BINDING PROTEIN; MESSENGER-RNA; PRETERM BIRTH; FETAL-GROWTH; CRH; STRESS; PLASMA

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.