Associations of Gestational Exposure to Air Pollution and Polycyclic Aromatic Hydrocarbons with Placental Inflammation

Abstract

Restricted fetal growth (RFG) is a leading contributor to perinatal mortality and has been associated with gestational exposure to air pollution, such as fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and polycyclic aromatic hydrocarbons (PAHs). This study examines the association between trimester-specific and weekly means of air pollution throughout gestation and placental inflammatory markers at delivery. In a prospective cohort study of 263 pregnant women in Rochester, NY, we measured interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in placental tissue and estimated gestational exposure to PM_2.5 and NO₂ using a high-resolution spatial-temporal model. Exposure to PAHs was estimated using urinary 1-hydroxypyrene (1-OHP) concentrations collected once per trimester. Using distributed lag models with a penalized spline function, each interquartile range (2.6 μg/m³) increase in PM_2.5 concentration during gestational weeks 6-11 was associated with decreased placental IL-6 levels (-22.2%, 95% CI: -39.0%, -0.64%). Using multiple linear regression models, each interquartile range increase of 1-OHP was associated with an increase in TNF-α in the first trimester (58.5%, 95% CI: 20.7%, 74.2%), third trimester (22.9%, 95% CI: 0.04%, 49.5%), and entire pregnancy (29.6%, 95%CI: 3.9%,60.6%). Our results suggest gestational exposure to air pollution may alter the inflammatory environment of the placenta at delivery.

Figure 1

Estimated distributed lag effect of PM_2.5 throughout pregnancy and placental inflammatory markers IL-6 (left panel) and TNF-α (right panel). Starting at gestational week 0, defined as the date of the last menstrual period or crown-rump length, depending on the participant, to gestational week 37. Adjusted for prepregnancy BMI, smoking during pregnancy, and maternal age. Lag effects are presented as the percent change in placental inflammatory marker per IQR increase of PM_2.5 (2.6 μg/m³) (N = 263).

Figure 2

Estimated distributed lag effect of NO₂ and placental inflammatory markers IL6 (left panel) and TNF-α (right panel). Starting at gestational week 0 defined as the date of the last menstrual period or crown-rump length depending on participant to gestational week 37. Adjusted for prepregnancy, BMI, smoking during pregnancy, and maternal age. Lag effects are presented as the percent change in placental inflammatory marker and 1 IQR increase of NO₂ (4.5 ppb). N = 263.

Figure 3

Associations of urinary 1-OHP concentrations with placental inflammatory marker IL-6 (left panel), and TNF-α (right panel). Associations were tested using linear models. All models were adjusted for smoking status, maternal age, and prepregnancy BMI. The association is presented as percent changes of 1-OHP concentrations per one interquartile increase in 1-OHP concentration, averaged over three trimesters: first, second, and third trimester. Significant was determined as p < 0.05.