Environment International (Apr 2025)
Periods of susceptibility for associations between phthalate exposure and preterm birth: Results from a pooled analysis of 16 US cohorts
- Alexa Friedman,
- Barrett M. Welch,
- Alexander P. Keil,
- Michael S. Bloom,
- Joseph M. Braun,
- Jessie P. Buckley,
- Dana Dabelea,
- Pam Factor-Litvak,
- John D. Meeker,
- Karin B. Michels,
- Vasantha Padmanabhan,
- Anne P. Starling,
- Clarice R. Weinberg,
- Jenny Aalborg,
- Akram N. Alshawabkeh,
- Emily S. Barrett,
- Alexandra M. Binder,
- Asa Bradman,
- Nicole R. Bush,
- Antonia M. Calafat,
- David E. Cantonwine,
- Kate E. Christenbury,
- José F. Cordero,
- Stephanie M. Engel,
- Brenda Eskenazi,
- Kim G. Harley,
- Russ Hauser,
- Julie B. Herbstman,
- Nina Holland,
- Tamarra James-Todd,
- Anne Marie Z. Jukic,
- Bruce P. Lanphear,
- Thomas F. McElrath,
- Carmen Messerlian,
- Roger B. Newman,
- Ruby H.N. Nguyen,
- Katie M. O’Brien,
- Virginia A. Rauh,
- J.Bruce Redmon,
- David Q. Rich,
- Emma M. Rosen,
- Sheela Sathyanarayana,
- Rebecca J. Schmidt,
- Amy E. Sparks,
- Shanna H. Swan,
- Christina Wang,
- Deborah J. Watkins,
- Barry Weinberger,
- Abby G. Wenzel,
- Allen J. Wilcox,
- Kimberly Yolton,
- Yu Zhang,
- Ami R. Zota,
- Kelly K. Ferguson
Affiliations
- Alexa Friedman
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
- Barrett M. Welch
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; University of Nevada, Reno, NV, USA
- Alexander P. Keil
- National Cancer Institute, Bethesda, MD, USA
- Michael S. Bloom
- George Mason University, Fairfax, VA, USA
- Joseph M. Braun
- Brown University, Providence, Rhode Island, USA
- Jessie P. Buckley
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Dana Dabelea
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Pam Factor-Litvak
- Columbia University, NY, USA
- John D. Meeker
- University of Michigan School of Public Health, Ann Arbor, MI, USA
- Karin B. Michels
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
- Vasantha Padmanabhan
- University of Michigan Medical School, Ann Arbor, MI, USA
- Anne P. Starling
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Clarice R. Weinberg
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
- Jenny Aalborg
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Akram N. Alshawabkeh
- Northeastern University, Boston, MA, USA
- Emily S. Barrett
- Rutgers School of Public Health, Piscataway, NJ, USA
- Alexandra M. Binder
- University of Hawaii Cancer Center, Honolulu, HI, USA
- Asa Bradman
- University of California, Merced, CA, USA
- Nicole R. Bush
- University of California, San Francisco, San Francisco, CA, USA
- Antonia M. Calafat
- National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
- David E. Cantonwine
- Brigham and Women’s Hospital, Boston, MA, USA
- Kate E. Christenbury
- DLH, LLC, Bethesda, MD, USA
- José F. Cordero
- University of Georgia, Athens, GA, USA
- Stephanie M. Engel
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Brenda Eskenazi
- University of California, Berkeley, CA, USA
- Kim G. Harley
- University of California, Berkeley, CA, USA
- Russ Hauser
- Harvard TH Chan School of Public Health, Boston, MA, USA
- Julie B. Herbstman
- Columbia University, NY, USA
- Nina Holland
- University of California, Berkeley, CA, USA
- Tamarra James-Todd
- Harvard TH Chan School of Public Health, Boston, MA, USA
- Anne Marie Z. Jukic
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
- Bruce P. Lanphear
- Simon Fraser University, Burnaby, British Columbia, Canada
- Thomas F. McElrath
- Brigham and Women’s Hospital, Boston, MA, USA
- Carmen Messerlian
- Harvard TH Chan School of Public Health, Boston, MA, USA
- Roger B. Newman
- Medical University of South Carolina, Charleston, SC, USA
- Ruby H.N. Nguyen
- University of Minnesota School of Public Health, Minneapolis, MN, USA
- Katie M. O’Brien
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
- Virginia A. Rauh
- Columbia University, NY, USA
- J.Bruce Redmon
- University of Minnesota Medical School, Minneapolis, MN, USA
- David Q. Rich
- University of Rochester Medical Center, Rochester, NY, USA
- Emma M. Rosen
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Sheela Sathyanarayana
- University of Washington and Seattle Children’s Research Institute, Seattle, WA, USA
- Rebecca J. Schmidt
- University of California, Davis, CA, USA
- Amy E. Sparks
- University of Iowa, Iowa City, IA, USA
- Shanna H. Swan
- Icahn School of Medicine at Mount Sinai, NY, USA
- Christina Wang
- The Lundquist Institute at Harbor, UCLA Medical Center, West Carson, CA, USA
- Deborah J. Watkins
- University of Michigan School of Public Health, Ann Arbor, MI, USA
- Barry Weinberger
- Cohen Children’s Medical Center of New York, Northwell Health, Queens, NY, USA
- Abby G. Wenzel
- University of Minnesota Medical School, Minneapolis, MN, USA
- Allen J. Wilcox
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
- Kimberly Yolton
- Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Yu Zhang
- Harvard TH Chan School of Public Health, Boston, MA, USA
- Ami R. Zota
- Columbia University, NY, USA
- Kelly K. Ferguson
- National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Corresponding author.
- Journal volume & issue
-
Vol. 198
p. 109392
Abstract
Background: Phthalate exposure during pregnancy has been associated with preterm birth, but mechanisms of action may depend on the timing of exposure. Objective: Investigate critical periods of susceptibility during pregnancy for associations between urinary phthalate metabolite concentrations and preterm birth. Methods: Individual-level data were pooled from 16 US cohorts (N = 6045, n = 539 preterm births). We examined trimester-averaged urinary phthalate metabolite concentrations. Most phthalate metabolites had 2248, 3703, and 3172 observations in the first, second, and third trimesters, respectively. Our primary analysis used logistic regression models with generalized estimating equations (GEE) under a multiple informant approach to estimate trimester-specific odds ratios (ORs) of preterm birth and significant (p < 0.20) heterogeneity in effect estimates by trimester. Adjusted models included interactions between each covariate and trimester. Results: Differences in trimester-specific associations between phthalate metabolites and preterm birth were most evident for di-2-ethylhexyl phthalate (DEHP) metabolites. For example, an interquartile range increase in mono (2-ethylhexyl) phthalate (MEHP) during the first and second trimesters was associated with ORs of 1.15 (95 % confidence interval [CI]: 0.99, 1.33) and 1.11 (95 % CI: 0.97, 1.28) for preterm birth, respectively, but this association was null in the third trimester (OR = 0.91 [95 % CI: 0.76, 1.09]) (p-heterogeneity = 0.03). Conclusion: The association of preterm birth with gestational biomarkers of DEHP exposure, but not other phthalate metabolites, differed by the timing of exposure. First and second trimester exposures demonstrated the greatest associations. Our study also highlights methodological considerations for critical periods of susceptibility analyses in pooled studies.
