Hormone concentrations mediate the associations between exposure to phthalate mixtures and preterm birth

Abstract

BACKGROUND AND AIM: Mixtures of phthalate compounds can be found in many consumer products, resulting in widespread human exposure. Previous work has suggested that phthalates display endocrine disrupting capabilities that may differ based on molecular weight of the parent compound, and are associated with preterm birth (PTB). Given the importance of hormone regulation during pregnancy, we hypothesized that phthalates may affect the timing of labor via disruption of hormone concentrations. We aimed to assess the mediating effects of hormone concentrations on the associations between phthalate mixtures and timing of delivery. METHODS: Urinary phthalate metabolite measurements were repeated up to 3 times, and serum hormone measurements up to 2 times, during mid-gestation, among 1011 women in the PROTECT (Puerto Rico Testsite for Exploring Contamination Threats) longitudinal birth cohort. We utilized ridge regression as a shrinkage and variable selection tool to create phthalate environmental risk scores (ERS) at each study visit for both low and high molecular weight (LMW, HMW) compounds, which represent a weighted sum of each individual’s exposure to the mixture of metabolites. Causal mediation analyses were then conducted on a subset of 705 women for whom hormone data was available. RESULTS:First visit testosterone and fT4 mediated 17.2% and 10.2%, respectively, of the association between LMW phthalate ERS and spontaneous PTB. When analyses were stratified by fetal sex, the association between LMW phthalate ERS and spontaneous PTB was mediated by CRH (28.8%), progesterone (17.6%), and testosterone (30.6%) among only pregnancies with a male fetus. Third visit CRH also mediated 38.3% of the association between HMW phthalate ERS and reduced gestational age at birth among only male fetuses. There were no significant mediating results observed for mothers carrying a female fetus. CONCLUSIONS:These results provide introductory evidence of hormone disruption on the causal pathway between phthalate exposure and preterm birth. KEYWORDS: endocrine disrupting chemicals, birth outcomes, mixtures analysis, mediation analysis