Phthalate metabolites and bisphenol-A in association with circulating angiogenic biomarkers across pregnancy.
BACKGROUND
Phthalates and bisphenol-a (BPA) are endocrine disrupting compounds with widespread exposure that have been linked to adverse birth outcomes and developmental effects. We hypothesized that these associations may be mediated in part through altered placental development and function consequent to exposure. To investigate this question, we examined associations between plasma biomarkers of angiogenesis and urinary biomarkers of exposure to phthalates and bisphenol-a (BPA) measured at repeated time points across pregnancy.


METHODS
We utilized a nested case-control population of 130 mothers who delivered preterm and 352 who delivered term from a prospective birth cohort. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in plasma samples collected from up to four visits during pregnancy (median 10, 18, 26, and 35 weeks). Phthalate metabolites and BPA were measured in urine samples collected at the same visits as indices of exposure.


RESULTS
In linear mixed effects models adjusted for urine dilution and gestational age at sample collection, oxidized di-2-ethylhexyl phthalate (DEHP) metabolites were associated with decreases in PlGF as well as increases in the sFlt-1 to PlGF ratio. These results were slightly attenuated in fully adjusted models. Other phthalate metabolites did not show consistent relationships with either sFlt-1 or PlGF. BPA, however, was associated with increased sFlt-1 as well as the sFlt-1 to PlGF ratio in both crude and adjusted models.


CONCLUSIONS
We observed associations between urinary DEHP metabolites and BPA and biomarkers of angiogenesis during pregnancy that may be indicative of disrupted placental development and/or function during gestation.
Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
K K
KK
Ferguson
Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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TF
McElrath
Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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DE
Cantonwine
Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
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B
Mukherjee
Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: meekerj@umich.edu.
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JD
Meeker
D001559:Benzhydryl Compounds / Q000652:urine*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D010636:Phenols / Q000652:urine*; D010795:Phthalic Acids / Q000652:urine*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D015415:Biomarkers; D010636:Phenols; D010795:Phthalic Acids; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1; C000608036:PGF protein, human; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Endocrine disrupting compounds; Environment; Epidemiology; Placenta; Preeclampsia