Urinary phthalate metabolites and biomarkers of oxidative stress in pregnant women: a repeated measures analysis.
BACKGROUND
Phthalate exposure occurs readily in the environment and has been associated with an array of health end points, including adverse birth outcomes. Some of these may be mediated by oxidative stress, a proposed mechanism for phthalate action.


OBJECTIVE
In the present study, we explored the associations between phthalate metabolites and biomarkers of oxidative stress measured in urine samples from multiple time points during pregnancy.


METHODS
Women were participants in a nested case-control study of preterm birth (n = 130 cases, n = 352 controls). Each was recruited early in pregnancy and followed until delivery, providing urine samples at up to four visits. Nine phthalate metabolites were measured to assess exposure, and 8-hydroxydeoxyguanosine and 8-isoprostane were also measured in urine as markers of oxidative stress. Associations were assessed using linear mixed models to account for intraindividual correlation, with inverse selection probability weightings based on case status to allow for greater generalizability.


RESULTS
Interquartile range increases in phthalate metabolites were associated with significantly higher concentrations of both biomarkers. Estimated differences were greater in association with monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), and monoisobutyl phthalate (MiBP), compared with di(2-ethylhexyl) phthalate (DEHP) metabolites.


CONCLUSIONS
Urinary phthalate metabolites were associated with increased oxidative stress biomarkers in our study population of pregnant women. These relationships may be particularly relevant to the study of birth outcomes linked to phthalate exposure. Although replication is necessary in other populations, these results may also be of great importance for a range of other health outcomes associated with phthalates.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Kelly K
KK
Ferguson
Thomas F
TF
McElrath
Yin-Hsiu
YH
Chen
Bhramar
B
Mukherjee
John D
JD
Meeker
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004785:Environmental Pollutants / Q000652:urine*; D005260:Female; D006801:Humans; D016014:Linear Models; D018384:Oxidative Stress / Q000502:physiology*; D010795:Phthalic Acids / Q000652:urine*; D011247:Pregnancy; D047928:Premature Birth / Q000652:urine
D015415:Biomarkers; D004785:Environmental Pollutants; D010795:Phthalic Acids; C075750:8-epi-prostaglandin F2alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine