Associations of urinary polycyclic aromatic hydrocarbon (PAH) metabolites and their mixture with thyroid hormone concentration during pregnancy in the LIFECODES cohort: A repeated measures study

Abstract

Background: Polycyclic aromatic hydrocarbons (PAHs) are endocrine disruptors resulting from incomplete combustion. Pregnancy represents a particularly vulnerable period to such exposures, given the significant influence of hormone physiology on fetal growth and pregnancy outcomes. Maternal thyroid hormones play crucial roles in fetal development and pregnancy outcomes. However, limited studies have examined gestational PAH exposure and maternal thyroid hormones during pregnancy.

Methods: Our study included 439 women enrolled in the LIFECODES birth cohort in Boston, aiming to explore the relationship between urinary PAH metabolites and thyroid hormones throughout pregnancy. Urine samples for PAH metabolite analysis and plasma samples for thyroid hormone were measured up to four visits throughout gestation. Single pollutant analyses employed linear mixed effect models to investigate individual associations between each PAH metabolite and thyroid hormone concentration. Sensitivity analyses were conducted to assess potential susceptibility windows and fetal-sex-specific effects of PAH exposure. Mixture analyses utilized quantile g-computation to evaluate the collective impact of eight PAH metabolites on thyroid hormone concentrations. Additionally, Bayesian kernel machine regression (BKMR) was employed to explore potential non-linear associations and interactions between PAH metabolites. Subject-specific random intercepts were incorporated to address intra-individual correlation of serial measurements over time in both single pollutant and mixture analyses.

Results: Our findings revealed positive trends in associations between PAH metabolites and thyroid hormones, both individually and collectively as a mixture. Sensitivity analyses indicated that these associations were influenced by the study visit and fetal sex. Mixture analyses suggested non-linear relationships and interactions between different PAH exposures.

Conclusions: This comprehensive investigation underscores the critical importance of understanding the impact of PAH exposures on thyroid hormone physiology during pregnancy. The findings highlight the intricate interplay between environmental pollutants and human pregnancy physiology, emphasizing the need for targeted interventions and public health policies to mitigate adverse outcomes associated with prenatal PAH exposure.

Keywords: Maternal exposure; Mixture; Polycyclic aromatic hydrocarbons; Thyroid.

Figure 1.

Linear mixed effect regression for thyroid hormone levels in association with urinary concentrations of PAHs (N=439 participants, 1368 samples). Forest plot depicting percent changes and 95% confidence intervals of thyroid hormones with interquartile range increase in PAH metabolites. Models were adjusted for gestational age, maternal age, education, race, insurance type, alcohol consumption, pre-pregnancy BMI, and specific gravity. PAH levels were natural log transformed.

Figure 2.

Multiple linear regressions of thyroid hormone versus urinary concentrations of PAH stratified by study visit (N_V1 =371; N_V2 =352; N_V3 =328; N_V4 =317). Forest plot depicting percent changes and 95% confidence intervals of thyroid hormones with interquartile range increase in PAH metabolites. Models were adjusted for maternal age, education, race, insurance type, alcohol consumption, pre-pregnancy BMI, and specific gravity. PAH levels were natural log transformed.

Figure 3.

Linear mixed effect regression for thyroid hormone levels in association with urinary concentrations of PAHs stratified by fetal sex. The number of participants and sample size for each group were as follows: N_all=439 (1368), N_female=199 (604), N_male=239 (762), N_missing=1 (2). Forest plot depicting percent changes and 95% confidence intervals of thyroid hormones with interquartile range increase in PAH metabolites. Models were adjusted for gestational age, maternal age, education, race, insurance type, alcohol consumption, pre-pregnancy BMI, and specific gravity. PAH levels were natural log transformed.

Figure 4.

Univariate exposure–response function (95% CI) between PAH metabolites and (a) T3 Thyroid hormone (b) T4 Thyroid hormone while fixing the concentrations of other PAHs at median values. Colors indicate the selection of PAH metabolites based on PIP>0.5 of BKMR models. Models were adjusted for maternal age, gestational age, education, race, insurance type, alcohol consumption, pre-pregnancy BMI, and specific gravity. PAH levels were natural log transformed.