Endocrine-Disrupting Chemicals and Persistent Nausea among Pregnant Women Enrolled in the Illinois Kids Development Study (I-KIDS).

Background: Pregnant women are exposed to numerous endocrine-disrupting chemicals (EDCs). Pregnancy-related nausea likely has hormonal etiology and may persist beyond the first trimester.

Objectives: Therefore, we aimed to determine the relationship between EDC biomarkers and pregnancy nausea characteristics.

Methods: Illinois Kids Development Study (I-KIDS) pregnant women ($n=467$) reported nausea symptoms monthly from conception to delivery. We categorized women as never having nausea (9%) or as having typical (ends by 17 wk gestation; 42%), persistent (ends after 17 wk gestation; 25%), or irregular (24%) nausea. Women provided five urine samples across pregnancy, which we pooled and analyzed for phthalate/replacement, phenol, and triclocarban biomarkers. Using covariate-adjusted logistic regression, we evaluated relationships of EDCs with nausea and used quantile-based g-computation (QGComp) and Bayesian kernel machine regression (BKMR) to evaluate joint associations of EDCs with nausea symptoms. We also considered differences in associations by fetal sex.

Results: Only the sum of urinary biomarkers of di(isononyl) cyclohexane-1,2-dicarboxylate ($\Sigma \text{DiNCH}$) was associated with higher risk of persistent nausea compared to typical nausea [odds ratio (OR) $=1.18$; 95% CI: 1.01, 1.37] in all women. However, using QGComp, a 10% higher concentration of the EDC mixture was associated with 14% higher risk of persistent nausea [relative risk (RR) $=1.14$; 95% CI: 1.01, 1.30], due to $\Sigma \text{DiNCH}$, ethylparaben, and the sum of di-2-ethylhexyl phthalate ($\Sigma \text{DEHP}$) metabolites. Similarly, using BMKR, the EDC mixture was associated with greater odds of persistent nausea in all women. In women carrying male offspring, ethylparaben was associated with persistent nausea, and a 10% higher concentration of the QGComp mixture was associated with 26% higher risk of persistent nausea ($\mathrm{RR}=1.26$; 95% CI:1.13, 1.41), driven by ethylparaben and $\Sigma \text{DiNCH}$. Consistently, using BKMR, EDCs were positively associated with persistent nausea in women carrying males. We did not identify associations between EDC biomarkers and persistent nausea in women carrying females or between EDC biomarkers and other nausea patterns.

Discussion: Nonpersistent EDCs, modeled as a mixture, are associated with persistent nausea in pregnancy, primarily in women carrying males. Future work should explore possible mechanisms, clinical implications, and interventions to reduce exposures and symptoms. https://doi.org/10.1289/EHP15547.