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.
Bibliographical noteFunding Information:
grants from the National Institutes of Health (NIH)/ National Institute of Environmental Health Sciences (NIEHS) and the US Environmental Protection Agency (EPA) during the conduct of the study; honorarium for grant review from the NIH/Center for Scientific Review outside the submitted work; and honorarium for advisory board participation from the University of Montana outside the submitted work. Dr Cordero reported grants from the NIH during the conduct of the study and outside the submitted work and from Medtronic Foundation outside the submitted work. Dr Barrett reported grants from NIH during the conduct of the study. Dr Bush reported grants from the NIH during the conduct of the study. Dr McElrath reported research support to their institution and equity from NxPrenatal Inc; serving on the scientific advisory board of and equity from Mirvie Inc; and serving on the scientific advisory board of and cash payment from Hoffmann-La Roche, Momenta Pharmaceuticals, Comanche Biopharma; and Tectonic Therapeutic. Dr Starling reported grants from the NIH during the conduct of the study. Dr Hauser reported grants from NIEHS during the conduct of the study. Dr Eskenazi reported grants from the NIH and EPA during the conduct of the study. Dr Harley reported grants from the NIEHS during the conduct of the study. Dr Holland reported grants from the NIEHS during the conduct of the study. Dr Bloom reported grants from the NIH during the conduct of the study. Dr Braun reported grants from the NIH during the conduct of the study and served as an expert witness for plaintiffs in litigation related to perfluoroalkyl substances–contaminated drinking water for Morgan & Morgan Law Firm (funds were not paid to Dr Braun directly; all compensation was paid to a discretionary account that cannot be used for salary or fringe) outside the submitted work. Dr Factor-Litvak reported grants from the NIH during the conduct of the study. Dr Jukic reported grants from the NIEHS during the conduct of the study. Dr Weinberg reported salary support from the NIEHS during the conduct of the study. Dr Weinberger reported grants from the NIH and the New Jersey Department of Environmental Protection during the conduct of the study. Dr Watkins reported grants from the NIH and EPA during the conduct of the study. Dr Schmidt reported grants from Autism Science Foundation during the conduct of the study. No other disclosures were reported.
Funding/Support: This research was supported
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PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural