Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts
Authors: Welch Barrett M. , Keil Alexander P. , Buckley Jessie P. , Calafat Antonia M. , Christenbury Kate E. , Engel Stephanie M. , O'Brien Katie M. , Rosen Emma M. , James-Todd Tamarra , Zota Ami R. , Ferguson Kelly K. ,   and the Pooled Phthalate Exposure and Preterm Birth Study Group
Published: March 2023

ABSTRACT
Preterm birth is a leading cause of neonatal mortality. Preterm birth is a public health burden, particularly in the United States, where approximately 10% of deliveries are preterm. Although the underlying cause of most preterm births is unknown, environmental chemical exposures (such as phthalates) possibly contribute. Phthalates are common in consumer products, and exposure can occur through diet, personal care products, and even household dust. Consequently, exposure is ubiquitous for pregnant individuals. Prenatal phthalate exposure has been associated with adverse neurodevelopment in children and disordered development of the male reproductive tract. This study reviewed 16 prospective studies conducted within the United States to pool individual-level data to examine prenatal urinary biomarkers of phthalate exposure and preterm birth. In addition, potential influence of exposure to overall phthalate mixture was assessed to determine the potential impact of reduced exposure on preterm birth.
Results of the study indicated that of 6045 pregnant women, 539 (9%) delivered preterm. Overall, of the entire included cohort, 802 individuals were Black (13.3%), 2576 were White (42.6%), 2323 were Latina (38.4%), and 328 had other race identity (including Native Hawaiian, Alaskan Native, or American Indian). Characteristics of participants were similar between those who delivered preterm versus term. Some 96% of urine samples displayed detectable concentrations of urinary phthalate metabolites. As demonstrated by regression analyses, higher concentrations of most phthalate metabolites bore an association of slightly higher odds (12%–16% higher) for preterm birth. In addition, the study estimated that reducing the mixture of phthalate metabolite concentrations by 10%, 30%, or 50%, respectively, could prevent 1.8, 5.9, and 11.1 preterm births per 1000 live births.
The study found a relationship between higher maternal pregnancy concentrations of urinary phthalate metabolites and preterm birth. The findings of this study identify a potential benefit of phthalate exposure reduction among pregnant individuals via either regulations or behavioral interventions. Because phthalate exposure can occur through many environments and sources, the US Consumer Product Safety Commission has attempted to pinpoint major sources of phthalate exposure and has determined that the predominate exposures appear to occur through food and medications, although uncertainty in the primary source of exposure remains. Phthalate exposure also widely varies in the United States based on several factors such as whether a person is at a disadvantaged socioeconomic status, is pregnant, or is of a marginalized race or ethnicity. Targeted interventions, such as altering personal care products, is made challenging as consumers are not readily able to access accurate ingredients lists. In the United States, for example, fragrance ingredient lists are not required to list phthalates when they are included in the product.
Diet interventions intending to reduce phthalate exposure have had mixed results. Although federally mandated restrictions have limited the use of phthalates in products for children, few such restrictions exist for products intended for pregnant individuals. As 28 phthalates are currently allowed as food additives or in food contact materials, they are difficult to avoid. Mitigation of population-level health effects from phthalates through regulatory means would be most effective when considering phthalates not as individual chemicals, but rather as a class.
This study found that higher concentrations of several urinary phthalate metabolites in pregnancy were associated with preterm birth, a consistent finding across 16 prospective US studies. Such findings emphasize the importance of the development of policy measures and public health around phthalate exposure reduction, especially among pregnant individuals.