Emily S Barrett1, Matthew Corsetti2, Drew Day3, Sally W Thurston2, Christine T Loftus4, Catherine J Karr5, Kurunthachalam Kannan6, Kaja Z LeWinn7, Alicia K Smith8, Roger Smith9, Frances A Tylavsky10, Nicole R Bush11, Sheela Sathyanarayana12. 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.
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.
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