Early pregnancy PM2.5 exposure and its inorganic constituents affect fetal growth by interrupting maternal thyroid function

Abstract

Early pregnancy is crucial for fetal growth. Maternal thyroid hormone is critical for fetal growth and can be disturbed under exogenous exposure. However, it's uncertain whether exposure to PM2.5 and inorganic constituents during early pregnancy can affect TH and fetal growth. We focused on the associations of early-pregnancy PM2.5 and inorganic constituents with fetal growth and maternal THs. PM2.5 concentration was estimated using a satellite-based spatiotemporal model. Fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), and humerus length (HL) were measured by ultrasonography at median 15.6, 22.2, and 33.1 gestational weeks. Levels of 28 PM2.5 constituents were measured in a sub-group of 329 pregnancies. Maternal serum free thyroxine (fT4), free triiodothyronine, and thyroid-stimulating hormone levels were measured at 14 weeks of gestation. Mixed-effect models and multiple linear regression were applied to evaluate the associations of PM2.5 and its constituents with fetal growth measures. Mediation analysis was used to examine the mediating role of the THs. Results showed that each 10 μg/m3 increase in PM2.5 was associated with 0.20 mm reductions in BPD (95%CI: 0.33, −0.01), 0.27 mm decreases in FL (95%CI: 0.40, −0.13), and 0.36 decreases in HL (95%CI: 0.49, −0.23). Per 10 μg/m3 increment in PM2.5 was correlated with 5.82% decreases in the fT4 level (95% CI: 8.61%, −2.96%). FT4 accounted for 14.3% of PM2.5 exposure-induced change in BPD at first follow-up. Al (β = −2.91, 95%CI: 5.17, −0.66), Si (β = −1.20, 95%CI: 2.22, −0.19), K (β = −3.09, 95%CI: 5.41, −0.77), Mn (β = −47.20, 95%CI: 83.68, −10.79) and Zn (β = −3.02, 95%CI: 5.55, −0.49) were associated with decreased fetal BPD, especially in first follow-up. Zn (β = −38.12%, 95% CI: 58.52%, −8.61%) was also associated with decreased fT4 levels. Overall, early pregnancy exposure to PM2.5 and its constituents was associated with fetal growth restriction and decreased maternal fT4 levels might mediate the effect of PM2.5.