Longitudinal associations between urinary biomarkers of phthalates and replacements with novel in vivo measures of placental health.

Autor:	Rosen EM; Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.; Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA., Stevens DR; Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA., McNell EE; Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.; Curriculum in Toxicology and Environmental Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA., Wood ME; Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA., Engel SM; Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA., Keil AP; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Calafat AM; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Botelho JC; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Sinkovskaya E; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA., Przybylska A; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA., Saade G; Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA., Abuhamad A; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA., Ferguson KK; Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Jazyk:	angličtina
Zdroj:	Human reproduction (Oxford, England) [Hum Reprod] 2024 Sep 01; Vol. 39 (9), pp. 2104-2114.
DOI:	10.1093/humrep/deae152
Abstrakt:	Study Question: What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes? Summary Answer: Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes. What Is Known Already: Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta. Study Design, Size, Duration: A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study. Participants/materials, Setting, Methods: At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models. Main Results and the Role of Chance: Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: -0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: -0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]). Limitations, Reasons for Caution: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance. Wider Implications of the Findings: We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function. Study Funding/competing Interest(s): This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services. Trial Registration Number: N/A. (Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology 2024.)
Databáze:	MEDLINE
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