Endocrine Disrupting Chemical Mixtures Alter Maternal Thyroid Hormones - A Potential Pathway for Altered Fetal Programming?

Abstract

Background: During early pregnancy the fetus wholly depends on maternal thyroid hormone (TH) for normal growth and development. Even sub-clinical changes can elicit adverse pregnancy and child-health outcomes. Individually, numerous endocrine disrupting chemicals (EDCs) have been linked to altered TH levels, but the combined effect of multiple EDCs remains understudied. Aim: To evaluate the cross-sectional association between 26 suspected or confirmed EDCs measured in urine and blood on maternal TH status during the first trimester of pregnancy. Methods: Within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study, we assessed EDCs in relation to thyroid function markers, including thyroxine and free and total triiodothyronine (fT3, tT3), among 1240 pregnant women (median 10 weeks gestation) using Weighted Quantile Sum (WQS) regression. We tested bi-directional constraints, adjusting for maternal age, ethnicity, education, parity, smoking, gestational age, thyroglobulin and thyroid-peroxidase antibodies, and urinary creatinine. Based on prior literature, we assessed interactions by gestational age. Results: The EDC mixture was related to lower fT3 levels (WQS=-0.21 95%CI=-0.29, -0.13); the largest chemical weights included total polychlorinated biphenyls (PCBs) (25%), trans-nonachlor (17%), and dichlorodiphenyltrichloroethane (DDT) (10%). The EDC mixture was related to altered fT3, with different chemicals eliciting positive and negative effects. The negatively constrained estimate (WQS=-0.12 95%CI=-0.19, -0.04) was driven by PCBs (17%), DDT (13%), and perfluorooctane sulfonate (PFOS) (13%), whereas the positively constrained estimate (WQS=0.08 95%CI=0.01, 0.15) was driven by 2-4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane-carboxylic-acid (MOiNCH) (13%), 2-hydroxyphenanthrene (12%), and monoethyl and monobutyl phthalates (MEP, MBP) (11%, 11%). With a negative constraint, there was a significant interaction between the EDC mixture and gestational age for fT3 (WQSxAge=-0.03 95%CI=-0.01, -0.05). Conclusions: During pregnancy, mixtures of persistent chlorinated and perfluoroalkyl compounds were related to lower tT3 and fT3, whereas short-lived pollutants (plasticizers, polycyclic aromatic hydrocarbon) were related to higher fT3. Detected associations may depend on gestational age.