Urinary phenol concentrations and fecundability and early pregnancy loss
Author:
Rosen Vollmar Ana K1ORCID, Weinberg Clarice R2, Baird Donna D3, Wilcox Allen J3, Calafat Antonia M4ORCID, Deziel Nicole C1, Johnson Caroline H1ORCID, Jukic Anne Marie Z3ORCID
Affiliation:
1. Environmental Health Sciences, Yale School of Public Health , New Haven, CT, USA 2. Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences , Research Triangle, NC, USA 3. Epidemiology Branch, National Institute of Environmental Health Sciences , Research Triangle, NC, USA 4. Organic Analytical Toxicology Branch, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA, USA
Abstract
Abstract
STUDY QUESTION
Are urinary phenol concentrations of methylparaben, propylparaben, butylparaben, triclosan, benzophenone-3, 2,4-dichlorophenol or 2,5-dichlorophenol associated with fecundability and early pregnancy loss?
SUMMARY ANSWER
2,5-dichlorophenol concentrations were associated with an increased odds of early pregnancy loss, and higher concentrations of butylparaben and triclosan were associated with an increase in fecundability.
WHAT IS KNOWN ALREADY
Phenols are chemicals with endocrine-disrupting potential found in everyday products. Despite plausible mechanisms of phenol reproductive toxicity, there are inconsistent results across few epidemiologic studies examining phenol exposure and reproductive function in non-fertility treatment populations.
STUDY DESIGN, SIZE, DURATION
Specimens and data were from the North Carolina Early Pregnancy Study prospective cohort of 221 women attempting to conceive naturally from 1982 to 1986. This analysis includes data from 221 participants across 706 menstrual cycles, with 135 live births, 15 clinical miscarriages and 48 early pregnancy losses (before 42 days after the last menstrual period).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants collected daily first-morning urine specimens. For each menstrual cycle, aliquots from three daily specimens across the cycle were pooled within individuals and analyzed for phenol concentrations. To assess sample repeatability, we calculated intraclass correlation coefficients (ICCs) for each phenol. We evaluated associations between phenol concentrations from pooled samples and time to pregnancy using discrete-time logistic regression and generalized estimating equations (GEE), and early pregnancy loss using multivariable logistic regression and GEE.
MAIN RESULTS AND THE ROLE OF CHANCE
ICCs for within-person variability across menstrual cycles in pooled phenol concentrations ranged from 0.42 to 0.75. There was an increased odds of early pregnancy loss with 2,5-dichlorophenol concentrations although the CIs were wide (5th vs 1st quintile odds ratio (OR): 4.79; 95% CI: 1.06, 21.59). There was an increased per-cycle odds of conception at higher concentrations of butylparaben (OR: 1.62; 95% CI: 1.08, 2.44) and triclosan (OR: 1.49; 95% CI: 0.99, 2.26) compared to non-detectable concentrations. No associations were observed between these endpoints and concentrations of other phenols examined.
LIMITATIONS, REASONS FOR CAUTION
Limitations include the absence of phenol measurements for male partners and a limited sample size, especially for the outcome of early pregnancy loss, which reduced our power to detect associations.
WIDER IMPLICATIONS OF THE FINDINGS
This study is the first to use repeated pooled measures to summarize phenol exposure and the first to investigate associations with fecundability and early pregnancy loss. Within-person phenol concentration variability underscores the importance of collecting repeated samples for future studies. Exposure misclassification could contribute to differences between the findings of this study and those of other studies, all of which used one urine sample to assess phenol exposure. This study also contributes to the limited literature probing potential associations between environmental exposures and early pregnancy loss, which is a challenging outcome to study as it typically occurs before a pregnancy is clinically recognized.
STUDY FUNDING/COMPETING INTEREST(S)
This research was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health (award number F31ES030594), the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (project numbers ES103333 and ES103086) and a doctoral fellowship at the Yale School of Public Health. The authors declare they have no competing interests to disclose.
TRIAL REGISTRATION NUMBER
N/A.
Funder
National Institute of Environmental Health Sciences of the National Institutes of Health NIH
Publisher
Oxford University Press (OUP)
Subject
Obstetrics and Gynecology,Rehabilitation,Reproductive Medicine
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