Relationships between levels of endocrine-disrupting chemicals and immune markers in maternal circulation during mid-pregnancy

Background and Aim: Prenatal exposure to endocrine-disrupting chemicals (EDCs) has been linked to child neurodevelopmental disorders. Maternal immune activation during pregnancy is associated with adverse child developmental outcomes. Whether EDCs influence maternal immune physiology is unclear. Methods: We analyzed data from general population controls (n=439) of the Early Markers for Autism (EMA) Study, a case-control study of children born during 2000-2003 in Southern California. Eleven polychlorinated biphenyls (PCBs), 6 brominated flame retardants (BFRs), 2 organochlorine pesticides (OCPs), 6 polyfluoroalkyl substances (PFAS), and 22 cytokines/chemokines were measured in maternal serum samples collected 15-20 weeks into pregnancy. We assessed individual relationships between log-transformed EDC levels and immune markers with spearman correlations and adjusted linear regression models. We further explored overall associations of EDC mixtures with specific immune markers using Bayesian kernel machine regression (BKMR). Results: After adjustment for false-discovery rate, 28 correlations between EDCs and maternal immune markers were statistically significant (spearman rho ranging from -0.25 to 0.24). These top correlations comprised 14 chemicals (9 PCBs, 3 PFAS, 1 BFR, and 1 OCP), and 8 immune markers. In adjusted linear models, all PCBs were inversely associated with levels of soluble interleukin-2 receptor alpha (sIL-2ra), with PCB99 showing the strongest relationship (adj-β[95%CI]: -0.48[-0.69, -0.27]). In BKMR, increasing all congeners in the PCB mixture from their 50th to their 95th percentiles was associated with decreased sIL-2ra (adj-β[95%CrI]: -0.43[-0.84, -0.02] and PCB99 had the highest relative importance in this mixture. Among other EDCs, p,p´-DDE, an OCP, was inversely associated with multiple markers (IL-12p40, IL-13, and IL-1ra). In contrast, others, such as Et-FOSAA, a PFAS, were positively associated with multiple immune markers, including IL-12p70, GM-CSF, IL-1ra, and IL-10. Conclusions: These findings suggest that specific EDCs may affect diverse immune and inflammatory pathways during pregnancy. These relationships may have implications for child development. Keywords: EDCs; prenatal; immune