Effects of prenatal exposure to air particulate matter on the risk of preterm birth and roles of maternal and cord blood LINE-1 methylation: A birth cohort study in Guangzhou, China

Abstract

Background: Epidemiological studies have found that increased risk of preterm birth (PTB) is associated with higher prenatal exposure to PM₁₀ and PM_2.5, but few studies have been conducted to assess the impacts of extremely fine particulate matter (PM₁) which may have more toxic effects than other types of ambient particulate air pollution (PM). Several studies have separately investigated the associations between DNA methylation and PTB risk and PM. Maternal LINE-1 methylation level negatively correlated with prenatal exposure to PM and risk of PTB. A comprehensive picture is lacking regarding the associations between prenatal exposure to PM, LINE-1 methylation, and risk of PTB.

Objectives: This study aimed to estimate the effects of exposure to ambient PM (PM₁₀, PM_2.5, and PM₁) of different sizes during pregnancy on risk of PTB, identify susceptible exposure windows, and illustrate the roles of LINE-1 methylation in the associations between PM and PTB risk.

Methods: The Birth Cohort Study on Prenatal Environments and Offspring Health (PEOH) has been ongoing since 2016 in Guangzhou, China. A total of 4928 pregnant women were recruited during early pregnancy, and 4278 (86.8%) were successfully followed-up. Each individual weekly exposure to PM₁₀ and PM_2.5 from 3 months before pregnancy to childbirth was assessed using a spatiotemporal land use regression model, and the weekly PM₁ exposure was estimated by employing a generalized additive model. Maternal and cord blood LINE-1 methylation levels (%5mC) were tested using bisulfite-PCR pyrosequencing. A distributed lag nonlinear model incorporated with a Cox proportional hazard model was applied to assess the effect of weekly-specific maternal PM exposure on PTB risk, and a multiple-linear regression model was employed to investigate the associations between PM exposure and LINE-1 methylation levels of maternal and cord bloods. We also assessed the associations between LINE-1 methylation levels and PTB risk by using a logistic regression model.

Results: The risk of PTB was positively associated with PM_2.5 and PM₁ concentrations during the 12th to 20th gestational weeks, and the strongest association was in the fourth quartile (Q₄) versus the first quartile (Q₁) and observed during the 16th gestational week (PM_2.5: harzard ratio [HR] = 1.18, 95%CI: 1.04-1.35, IQR = 11.94 μg/m³. PM₁: HR = 1.20, 95%CI: 1.03-1.39, IQR = 11.36 μg/m³). We observed significantly negative associations of PM₁₀(β = -0.51%5mC per 10 μg/m³, P = 0.014), PM_2.5 (β = -0.66%5mC per 10 μg/m³, P = 0.032) and PM₁ (β = -0.67%5mC per 10 μg/m³, P = 0.032) concentrations with cord blood LINE-1 methylation levels, and a negative association between PM₁ concentration and maternal LINE-1 methylation level (β = -0.86%5mC per 10 μg/m³, P = 0.034).

Conclusion: Higher prenatal exposure to PM₁ and PM_2.5 during the 12th to 20th gestational weeks was associated with increased risk of PTB. Maternal and fetal LINE-1 methylation alternation might be an underlying mechanism of PM that increasing the risk of PTB.

Keywords: Birth cohort study; LINE-1 methylation; Particulate matter; Preterm birth; Susceptible exposure window.