Effect Modification by Socioeconomic Status on the Associations between Early Placental Protein Damage and Exposure to Ambient Air PM2.5 Chemical Components

Abstract

Background: Ambient fine particulate matter with aerodynamic diameter $\le 2.5\mu m$ (${\mathrm{PM}}_{2.5}$) exposure is associated with systemic protein damage in pregnant women. However, its effect on protein damage in human placentas is unclear.

Objectives: We estimated the associations of ${\mathrm{PM}}_{2.5}$ and chemical component exposures with advanced oxidation protein products (AOPP) in placental villi tissues before 13 weeks of gestation.

Methods: We enrolled 165 women with unintended normal early pregnancy (NEP) who requested induced abortion during the first trimester and 165 women with early pregnancy loss (EPL) who also requested induced abortion (2017-2022). Maternal daily ${\mathrm{PM}}_{2.5}$, black carbon (BC), organic matter (OM), sulfate, nitrate, and ammonium exposures from the 12th week before ovulation to villi collection were estimated using data accessed from the Tracking Air Pollution in China platform. Associations of pollutant exposures during the 30 days before villi collection, during the post-conception period (from ovulation to villi collection), and during the periovulatory period (from the 12th week before to the third week after ovulation) with villi AOPP were estimated and compared between the NEP and EPL groups. Additionally, effect modifications by socioeconomic status expressed in family monthly income per capita were estimated using stratified distributed lag nonlinear models.

Results: Thirty-day cumulative and average post-conception exposures to higher concentrations of ${\mathrm{PM}}_{2.5}$, BC, and OM were associated with higher villi AOPP in all subjects and both groups. Thirty-day cumulative effects of per interquartile range increase in the residuals of BC and OM were robust in EPL [$\beta$ values (95% confidence interval) of villi AOPP were 111.22% (17.96%, 278.24%) and 93.87% (20.63%, 211.56%)] but were not robust in NEP. The associations of per interquartile range increase in the concentrations of BC and OM at some lag days with higher villi AOPP were stronger in low-income stratification (the ranges of $\beta$ values of villi AOPP were 10.51-11.99% and 8.08-12.50%) than those in medium-income stratification (3.19-3.80% and 1.95-3.73%) and high-income stratification (2.57-2.78% and 2.51-2.72%). Periovulatory OM exposure was positively associated with villi AOPP in EPL but not in NEP, and the susceptible periods to ${\mathrm{PM}}_{2.5}$ and the other four components were 1-4 weeks earlier in EPL than in NEP.

Discussion: Maternal ${\mathrm{PM}}_{2.5}$, BC, and OM exposures were positively associated with oxidative protein damage in early placenta. The associations were stronger in women with EPL or low-income. https://doi.org/10.1289/EHP15170.

Figure 1.

Daily distributed lag associations of per interquartile range increase in the concentrations of ${\mathrm{PM}}_{2.5}$ (A), BC (B), OM (C), ${\mathrm{SO}}_4^{2–}$ (D), ${\mathrm{NO}}_3^{–}$ (E), and ${\text{NH}}_4^{+}$ (F) at lag 0–30 with differences in villi AOPP (%) in all subjects ($n=330$). Note: The IQRs of ${\mathrm{PM}}_{2.5}$, BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ concentrations in the analyses were 33, 1.5, 8.1, 5.4, 7.7, and $4.7{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, respectively. The independent variables in the distributed lag nonlinear models combined with multivariable linear regression models simultaneously included every daily exposure to ${\mathrm{PM}}_{2.5}$ or each component at lag 0–30, all demographic characteristics presented in Table 1, temperature, relative humidity, and group (EPL or NEP). Numeric data for Figure 1 can be found in Excel Table S1. AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; ${\text{NH}}_4^{+}$, ammonium; ${\mathrm{NO}}_3^{–}$, nitrate; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{SO}}_4^{2–}$, sulfate.

Figure 2.

Daily distributed lag associations of per interquartile range in the residuals of BC (A), OM (B), ${\mathrm{SO}}_4^{2–}$ (C), ${\mathrm{NO}}_3^{–}$ (D), and ${\text{NH}}_4^{+}$ (E) at lag 0–30 with differences in villi AOPP (%) in all subjects ($n=330$). Note: The IQRs of BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ residuals were 0.19, 0.17, 0.49, 0.84, and 0.76, respectively. The independent variables in the distributed lag nonlinear models combined with multivariable linear regression models simultaneously included every daily residual of each chemical component at lag 0–30, all demographic characteristics presented in Table 1, temperature, relative humidity, and group (EPL or NEP). Numeric data for Figure 2 can be found in Excel Table S2. AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; ${\text{NH}}_4^{+}$, ammonium; ${\mathrm{NO}}_3^{–}$, nitrate; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{SO}}_4^{2–}$, sulfate.

Figure 3.

Daily distributed lag associations of per interquartile range increase in the concentrations of ${\mathrm{PM}}_{2.5}$ (A), BC (B), OM (C), and ${\mathrm{SO}}_4^{2–}$ (D) at lag 0–30 with differences in villi AOPP (%) in stratifications of low income ($n=84$), medium income ($n=111$), and high income ($n=135$). Note: The IQRs of ${\mathrm{PM}}_{2.5}$, BC, OM, and ${\mathrm{SO}}_4^{2–}$ concentrations in the analyses were 33, 1.5, 8.1, and $5.4{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, respectively. The independent variables in the distributed lag nonlinear models combined with multivariable linear regression models simultaneously included every daily exposure to ${\mathrm{PM}}_{2.5}$, BC, OM, or ${\mathrm{SO}}_4^{2–}$ at lag 0–30, all demographic characteristics presented in Table 1, temperature, relative humidity, and group (EPL or NEP). Numeric data for Figure 3 can be found in Excel Table S3. AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{SO}}_4^{2–}$, sulfate.

Figure 4.

Thirty-day cumulative associations of per interquartile range increase in the concentrations of ${\mathrm{PM}}_{2.5}$ and chemical components with differences in villi AOPP (%) in stratifications of low income ($n=84$), medium income ($n=111$), and high income ($n=135$). Note: The IQRs of ${\mathrm{PM}}_{2.5}$, BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ concentrations in the analyses were 33, 1.5, 8.1, 5.4, 7.7, and $4.7{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, respectively. The independent variables in the distributed lag nonlinear models combined with multivariable linear regression models simultaneously included every daily exposure to ${\mathrm{PM}}_{2.5}$ or each component at lag 0–30, all demographic characteristics presented in Table 1, temperature, relative humidity, and group (EPL or NEP). Numeric data for Figure 4 can be found in Table S4. AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; ${\text{NH}}_4^{+}$, ammonium; ${\mathrm{NO}}_3^{–}$, nitrate; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; SES, socioeconomic status; ${\mathrm{SO}}_4^{2–}$, sulfate.

Figure 5.

Associations of per interquartile range increase in the concentrations (A) and residuals (B) of average ${\mathrm{PM}}_{2.5}$ and chemical components during the post-conception period (from ovulation to villi collection) with differences in villi AOPP (%) in all subjects ($n=330$), EPL ($n=165$), and NEP ($n=165$). Note: The IQRs of ${\mathrm{PM}}_{2.5}$, BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ concentrations in the analyses were 33, 1.5, 8.1, 5.4, 7.7, and $4.7{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, respectively. The IQRs of BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ residuals were 0.19, 0.17, 0.49, 0.84, and 0.76, respectively. The independent variables in the multivariable linear regression models included average concentration of ${\mathrm{PM}}_{2.5}$ or each component during the postconception period in panel A, replaced by residual of each component during the postconception period in panel B, and also included all demographic characteristics presented in Table 1, temperature, relative humidity, and group (EPL or NEP). Numeric data for Figure 5 can be found in Table S6. AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; ${\text{NH}}_4^{+}$, ammonium; ${\mathrm{NO}}_3^{–}$, nitrate; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{SO}}_4^{2–}$, sulfate.

Figure 6.

Weekly distributed lag associations of per interquartile range increase in the concentrations of ${\mathrm{PM}}_{2.5}$ (A), BC (B), OM (C), ${\mathrm{SO}}_4^{2–}$ (D), ${\mathrm{NO}}_3^{–}$ (E), and ${\text{NH}}_4^{+}$ (F) during the periovulatory period with differences in villi AOPP (%) in all subjects ($n=330$). Note: The IQRs of ${\mathrm{PM}}_{2.5}$, BC, OM, ${\mathrm{SO}}_4^{2–}$, ${\mathrm{NO}}_3^{–}$, and ${\text{NH}}_4^{+}$ concentrations in the analyses were 33, 1.5, 8.1, 5.4, 7.7, and $4.7{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$, respectively. The independent variables in the distributed lag nonlinear models combined with multivariable linear regression models simultaneously included 15 weekly ${\mathrm{PM}}_{2.5}$ or each component concentrations, all demographic characteristics presented in Table 1, and group (EPL or NEP). Numeric data for Figure 6 can be found in Excel Tables S4. _A, week after ovulation; _B, week before ovulation; AOPP, advanced oxidation protein product; BC, black carbon; EPL, early pregnancy loss; IQR, interquartile range; NEP, normal early pregnancy; ${\text{NH}}_4^{+}$, ammonium; ${\mathrm{NO}}_3^{–}$, nitrate; OM, organic matter; ${\mathrm{PM}}_{2.5}$, particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$; ${\mathrm{SO}}_4^{2–}$, sulfate.