Exposures to Phthalate Mixtures are Associated with Adverse Birth Outcomes in a Puerto Rico Pregnancy Cohort

Abstract

Phthalates are synthetic chemicals used many consumer products. Humans are exposed to complex mixtures of phthalates from diverse sources. Previous studies have reported significant associations between individual phthalate metabolites and adverse birth outcomes such as preterm birth (PTB), but research on how mixtures of phthalates may be related to these outcomes is limited. We utilized data from the PROTECT prospective pregnancy cohort in Puerto Rico, in which 884 women provided up to three urine samples throughout gestation (median 18, 22, and 26 weeks). Samples were analyzed for 13 phthalate metabolites, and birth outcome data (PTB and spontaneous PTB, gestational age, small and large for gestational age (SGA, LGA), and birth weight z-score) were abstracted from medical records. We utilized adaptive elastic net (adENET) to determine which phthalate metabolites in the mixture were most predictive of each birth outcome. We then utilized weights from adENET to construct environmental risk scores (ERS), which represent a weighted sum of each woman’s exposure to the phthalate mixture. Birth outcomes were then regressed on quartiles of ERS. We assessed visit-specific and gestational average ERS associations, and explored whether birth outcomes differed by fetal sex. The highest quartile of average ERS was associated with 2.21 times (95% CI: 1.01, 4.81) greater odds of PTB, and 3.13 (95% CI: 1.14, 8.56) times greater odds of spontaneous PTB, relative to the lowest ERS quartile. Exposures at the second study visit were strongest in relation to odds of PTB, while third visit exposures were strongest for spontaneous PTB. Spontaneous PTB results remained significant among male fetuses, while female results were attenuated. The highest quartile of ERS was associated with increased odds of LGA and reduced birth weight z-score among both male and female fetuses. These results highlight the need to study complex mixtures to better understand true health risks.