Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Barrett M Welch; Alexander P Keil; Jessie P Buckley; Antonia M Calafat; Kate E Christenbury; Stephanie M Engel; Katie M O'Brien; Emma M Rosen; Tamarra James-Todd; Ami R Zota; Kelly K Ferguson; Pooled Phthalate Exposure and Preterm Birth Study Group; Akram N Alshawabkeh; José F Cordero; John D Meeker; Emily S Barrett; Nicole R Bush; Ruby H N Nguyen; Sheela Sathyanarayana; Shanna H Swan; David E Cantonwine; Thomas F McElrath; Jenny Aalborg; Dana Dabelea; Anne P Starling; Russ Hauser; Carmen Messerlian; Yu Zhang; Asa Bradman; Brenda Eskenazi; Kim G Harley; Nina Holland; Michael S Bloom; Roger B Newman; Abby G Wenzel; Joseph M Braun; Bruce P Lanphear; Kimberly Yolton; Pam Factor-Litvak; Julie B Herbstman; Virginia A Rauh; Erma Z Drobnis; Amy E Sparks; J Bruce Redmon; Christina Wang; Alexandra M Binder; Karin B Michels; Donna D Baird; Anne Marie Z Jukic; Clarice R Weinberg; Allen J Wilcox; David Q Rich; Barry Weinberger; Vasantha Padmanabhan; Deborah J Watkins; Irva Hertz-Picciotto; Rebecca J Schmidt

doi:10.1001/jamapediatrics.2022.2252

Lifestyle and Environment Environmental Exposures

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Welch BM, Keil AP, Buckley JP, Calafat AM, Christenbury KE, Engel SM, O'Brien KM, Rosen EM, James-Todd T, Zota AR, Ferguson KK, Pooled Phthalate Exposure and Preterm Birth Study Group, Alshawabkeh AN, Cordero JF, Meeker JD, Barrett ES, Bush NR, Nguyen RHN, Sathyanarayana S, Swan SH, Cantonwine DE, McElrath TF, Aalborg J, Dabelea D, Starling AP, Hauser R, Messerlian C, Zhang Y, Bradman A, Eskenazi B, Harley KG, Holland N, Bloom MS, Newman RB, Wenzel AG, Braun JM, Lanphear BP, Yolton K, Factor-Litvak P, Herbstman JB, Rauh VA, Drobnis EZ, Sparks AE, Redmon JB, Wang C, Binder AM, Michels KB, Baird DD, Jukic AMZ, Weinberg CR, Wilcox AJ, Rich DQ, Weinberger B, Padmanabhan V, Watkins DJ, Hertz-Picciotto I, Schmidt RJ

Published September 2022 JAMA pediatrics, 176(9), 895-905

DOI 10.1001/jamapediatrics.2022.2252 PMID 35816333 PMC PMC9274448

Abstract

Importance

Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.

Objective

To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.

Design, Setting, and Participants

Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.

Exposures

Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.

Main Outcomes and Measures

Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.

Results

The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.

Conclusions and Relevance

Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Topics

Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals · Pregnancy › Preterm Birth › Prediction · Birth and Delivery › Birth Outcomes › Maternal Morbidity

Barrett M Welch, Alexander P Keil, Jessie P Buckley, Antonia M Calafat, Kate E Christenbury, Stephanie M Engel, Katie M O'Brien, Emma M Rosen, Tamarra James-Todd, Ami R Zota, Kelly K Ferguson, Akram N Alshawabkeh, José F Cordero, John D Meeker, Emily S Barrett, Nicole R Bush, Ruby H N Nguyen, Sheela Sathyanarayana, Shanna H Swan, David E Cantonwine, Thomas F McElrath, Jenny Aalborg, Dana Dabelea, Anne P Starling, Russ Hauser, Carmen Messerlian, Yu Zhang, Asa Bradman, Brenda Eskenazi, Kim G Harley, Nina Holland, Michael S Bloom, Roger B Newman, Abby G Wenzel, Joseph M Braun, Bruce P Lanphear, Kimberly Yolton, Pam Factor-Litvak, Julie B Herbstman, Virginia A Rauh, Erma Z Drobnis, Amy E Sparks, J Bruce Redmon, Christina Wang, Alexandra M Binder, Karin B Michels, Donna D Baird, Anne Marie Z Jukic, Clarice R Weinberg, Allen J Wilcox, David Q Rich, Barry Weinberger, Vasantha Padmanabhan, Deborah J Watkins, Irva Hertz-Picciotto, Rebecca J Schmidt

B Welch, Alex Keil, A Keil, J Buckley, A Calafat, Catherine Christenbury, Katherine Christenbury, Kathryn Christenbury, K Christenbury, S Engel, Katherine O'Brien, K O'Brien, E Rosen, T James-Todd, A Zota, K Ferguson, A Alshawabkeh, J Cordero, Jack Meeker, J Meeker, E Barrett, N Bush, R Nguyen, S Sathyanarayana, S Swan, Dave Cantonwine, D Cantonwine, Tom McElrath, T McElrath, Jennifer Aalborg, J Aalborg, D Dabelea, A Starling, R Hauser, C Messerlian, Y Zhang, A Bradman, B Eskenazi, K Harley, N Holland, Mike Bloom, M Bloom, R Newman, Abigail Wenzel, A Wenzel, Joe Braun, Joey Braun, J Braun, B Lanphear, K Yolton, P Factor-Litvak, J Herbstman, V Rauh, E Drobnis, A Sparks, C Wang, Alex Binder, A Binder, K Michels, D Baird, A Jukic, C Weinberg, A Wilcox, Dave Rich, D Rich, B Weinberger, V Padmanabhan, Debbie Watkins, Deb Watkins, D Watkins, I Hertz-Picciotto, Becky Schmidt, R Schmidt

PMID 35816333 35816333 DOI 10.1001/jamapediatrics.2022.2252 10.1001/jamapediatrics.2022.2252 Welch et al. 2022, Welch 2022

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Abstract

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