The roles of endocrine disrupting chemicals and maternal hardships on adverse pregnancy outcomes

Background: Prenatal exposure to endocrine disrupting chemicals (EDCs), both individually and as mixtures, may affect pregnancy outcomes. The evidence on the relationships of phthalate exposure with preterm birth (PTB) and EDC mixtures with infant birth weight, however, remain inconsistent. Furthermore, the joint effects of EDC exposures and maternal hardships are underexplored. Objectives: We assessed (1) the relationship between prenatal exposure to phthalates and PTB, (2) the relationship between prenatal exposure to EDC mixture by class and birth weight, and (3) the modifying effect of maternal hardships on the relationship between prenatal exposure to EDCs and birth weight. Methods: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of approximately 2000 pregnant women enrolled between 2008 and 2011. We quantified EDC concentrations in urine or blood samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound and birth weight was obtained from medical records. Maternal hardships were assessed via an interview questionnaire. Cox Proportional-Hazard models were used to examine the associations of phthalate metabolite concentrations with time to delivery before 37 weeks of gestation and Bayesian kernel machine regression models were used to explore EDC mixture effects. To study the modifying effects of maternal hardships, we first used elastic net regression to identify the most important EDCs, maternal hardships and 2-way interactions between maternal hardships and EDCs. Subsequently, we used linear regression to obtain the unbiased estimates and plotted the relationships by hardship status for visual interpretation. Results: We found no evidence of an association between phthalate metabolite concentrations and PTB but found evidence that mixtures of organochlorine compounds (OCs) and metals were associated with mean birth weight reduction. trans-Nonachlor from the OC mixture and lead from the metal mixture had the greatest impact on birth weight. A reduction of approximately 40 grams were observed for every 2-fold increase in both EDC concentrations. Furthermore, we found that maternal hardships modified the strength and the direction of the relationships between prenatal exposure to EDCs and birth weight. Conclusions: Among the MIREC population, phthalate exposure during early pregnancy was not associated with the risk of PTB but OC and metal mixtures were associated with reduced birth weight. Maternal hardships may modify the relationships between prenatal exposure to EDCs and fetal growth.