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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. 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. 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. 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. • Polycyclic aromatic hydrocarbons (PAHs) exposure and thyroid hormone levels were assessed up to four times during pregnancy. • Gestational exposure to PAHs was associated with thyroid hormone concentration during pregnancy. • Associations between PAHs and thyroid hormone concentration varied based on study visit and fetal sex. • Certain PAHs exhibited non-linear associations with thyroid hormones and interacted with other PAHs. [ABSTRACT FROM AUTHOR]

Background: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery.Methods and Findings: Our data come from a case-control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women's Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m2). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%-97% higher among SGA cases and 33%-39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth.Conclusions: In this nested case-control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes. [ABSTRACT FROM AUTHOR]

Exposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population. To study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions. We estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the "essential" PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals. We observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned. • We examined associations between urinary trace metals and oxidative stress in pregnancy. • Higher oxidative stress was observed with increasing levels of urinary selenium. • Higher oxidative stress was also observed with increasing levels of urinary copper. • Increasing cumulative trace metals was also associated with higher oxidative stress. [ABSTRACT FROM AUTHOR]