Considerations for the Analysis of Urinary Environmental Chemical Concentrations During Pregnancy

Authors

• Danielle R. Stevens, University of North Carolina-Chapel Hill
• Kaleigh Hinton, University of North Carolina-Chapel Hill
• Katie M. O'Brien, University of North Carolina-Chapel Hill
• Jessie P. Buckley, National Institute of Environmental Health Sciences, Durham, N.C.
• Barrett M. Welch, University of North Carolina- Chapel Hill
• Jason A. Watts, National Institute of Environmental Health Sciences, Durham, N.C.
• Antonia M. Calafat, Centers for Disease Control and Prevention, Atlanta, Georgia
• Julianne C. Botelho, Centers for Disease Control and Prevention, Atlanta, Georgia
• Elena Sinkovskaya, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Ann Przybylska, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• George Saade, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Alfred Abuhamad, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Kelly K. Ferguson, National Institute of Environmental Health Sciences

ORCID

0000-0002-1529-2259 (Przybylska), 0009-0000-5433-4573 (Abuhamad)

Document Type

Article

Publication Date

2026

DOI

10.1097/ede.0000000000001960

Publication Title

Epidemiology

Volume

37

Issue

3

Pages

325-335

Abstract

Background:

Pregnancy physiology may impact indicators of hydration, affecting exposure assessment in gestational studies with urinary chemical biomarkers.

Methods:

We aimed to characterize hydration and demonstrate the impact of different methods for standardizing urinary chemical biomarker concentrations on exposure descriptives in the Human Placenta and Phthalates Study (n = 303, 2017-2020), a prospective pregnancy cohort with eight study visits between 12 and 38 weeks of gestation. We assessed trajectories and predictors of hydration using urine flow rate (UFR) and specific gravity (SG). Likewise, we examined trajectories and predictors of mono-n-butyl phthalate (MBP), for which concentrations were unstandardized or standardized via UFR (analyte excretion rates), SG alone (Boeniger method), or covariate-adjusted SG (O'Brien method). We used generalized additive mixed effects models to examine trajectories. We used linear mixed effects models to investigate participant demographic and pregnancy characteristics influencing UFR and SG, and agreement between unstandardized and standardized MBP concentrations.

Results:

As pregnancy progressed, SG declined linearly, whereas UFR varied in a nonlinear manner. Several demographic and pregnancy characteristics, notably race and ethnicity, were associated with UFR and SG. Unstandardized and standardized MBP concentrations showed good agreement, with lower agreement observed between concentrations standardized using UFR (analyte excretion rates) relative to SG (Boeniger and O'Brien methods). Nevertheless, trajectories and predictors of MBP concentrations were similar across all standardization approaches.

Conclusions:

Despite systematic variations in hydration across gestation and by demographic and pregnancy characteristics, methods commonly used for standardizing urinary concentrations of chemical biomarkers were robust to differences in the hydration indicator as well as the standardization method employed.

Rights

© 2026 The Authors

Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government. Foreign copyright may apply.

Original Publication Citation

Stevens, D. R., Hinton, K., O'Brien, K. M., Buckley, J. P., Welch, B. M., Watts, J. A., Calafat, A. M., Botelho, J. C., Sinkovskaya, E., Przybylska, A., Saade, G., Abuhamad, A., & Ferguson, K. K. (2026). Considerations for the analysis of urinary environmental chemical concentrations during pregnancy. Epidemiology, 37(3), 325-335. https://doi.org/10.1097/ede.0000000000001960

Repository Citation

Stevens, D. R., Hinton, K., O'Brien, K. M., Buckley, J. P., Welch, B. M., Watts, J. A., Calafat, A. M., Botelho, J. C., Sinkovskaya, E., Przybylska, A., Saade, G., Abuhamad, A., & Ferguson, K. K. (2026). Considerations for the analysis of urinary environmental chemical concentrations during pregnancy. Epidemiology, 37(3), 325-335. https://doi.org/10.1097/ede.0000000000001960