Preconceptional and the first trimester exposure to PM2.5 and offspring neurodevelopment at 24 months of age: Examining mediation by maternal thyroid hormones in a birth cohort study

Prenatal fine particulate matter (PM₂.₅) exposure has been associated with impaired offspring neurodevelopment; however, the association of PM₂.₅ exposure during preconception with offspring’s neurodevelopment and factors responsible for this association are still unclear. This study estimated the associations of PM₂.₅ exposure during preconception and the first trimester with offspring neurodevelopment and evaluated whether maternal thyroid hormones mediate these associations. We recruited 1329 mother-child pairs between 2013 and 2015 in Wuhan, China. PM₂.₅ exposure levels of each woman during the 3 months preconception and the first trimester were estimated using land-use regression models. Offspring neurodevelopment characterized by mental developmental index (MDI) and psychomotor developmental index (PDI) were measured at 24 months of age. Maternal serum levels of free thyroxine (FT3), free triiodothyronine (FT4), and thyroid-stimulating hormone (TSH) during early pregnancy were measured of a subset of the 1329 women (551 women). Generalized estimation equation and general linear regression models were used to estimate the associations between maternal PM₂.₅ exposure, thyroid hormones, and offspring neurodevelopment. After adjusting for potential confounders, we found that either among all participants or the subset, PM₂.₅ exposure during preconception and the first trimester was negatively associated with offspring PDI. Double increment in the first trimester PM₂.₅ exposure was significantly associated with 3.43 and 6.48 points decrease in offspring MDI. In the subset, each doubling of PM₂.₅ exposure during preconception and the first trimester was significantly associated with 7.93 and 8.02 points decrease in maternal FT4 level, respectively. Increased maternal FT4, in turn, was associated with increased PDI (β = 16.69, 95% CI: 5.39, 27.99). About 7.7% (95% CI: 2.0%–19.4%) and 8.6% (95% CI: 3.0%, 22.1%) of the effect of PM₂.₅ exposure during preconception on offspring PDI was mediated through maternal FT4 and the FT4/FT3 ratio, respectively.