%0 Journal Article
%T Longitudinal associations between urinary biomarkers of phthalates and replacements with novel in vivo measures of placental health.
%A Rosen EM
%A Stevens DR
%A McNell EE
%A Wood ME
%A Engel SM
%A Keil AP
%A Calafat AM
%A Botelho JC
%A Sinkovskaya E
%A Przybylska A
%A Saade G
%A Abuhamad A
%A Ferguson KK
%J Hum Reprod
%V 0
%N 0
%D 2024 Jul 6
%M 38970902
%F 6.353
%R 10.1093/humrep/deae152
%X <B>OBJECTIVE: </B>What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes?<BR><B>CONCLUSIONS: </B>Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes.<BR><B>BACKGROUND: </B>Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta.<BR><B>METHODS: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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]).<BR><B>CONCLUSIONS: </B>Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance.<BR><B>CONCLUSIONS: </B>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.<BR><B>BACKGROUND: </B>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.<BR><B>BACKGROUND: </B>N/A.