Prenatal Exposure to Ambient Air Pollution and Epigenetic Aging at Birth in Newborns

Abstract

In utero air pollution exposure has been associated with adverse birth outcomes, yet effects of air pollutants on regulatory mechanisms in fetal growth and critical windows of vulnerability during pregnancy are not well understood. There is evidence that epigenetic alterations may contribute to these effects. DNA methylation (DNAm) based age estimators have been developed and studied extensively with health outcomes in recent years. Growing literature suggests environmental factors, such as air pollution and smoking, can influence epigenetic aging. However, little is known about the effect of prenatal air pollution exposure on epigenetic aging. In this study, we leveraged existing data on prenatal air pollution exposure and cord blood DNAm from 332 mother-child pairs in the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), two pregnancy cohorts enrolling women who had a previous child diagnosed with autism spectrum disorder, to assess the relationship of prenatal exposure to air pollution and epigenetic aging at birth. DNAm age was computed using existing epigenetic clock algorithms for cord blood tissue—Knight and Bohlin. Epigenetic age acceleration was defined as the residual of regressing chronological gestational age on DNAm age, accounting for cell type proportions. Multivariable linear regression models and distributed lag models (DLMs), adjusting for child sex, maternal race/ethnicity, study sites, year of birth, maternal education, were completed. In the single-pollutant analysis, we observed exposure to PM2.5, PM10, and O3 during preconception period and pregnancy period were associated with decelerated epigenetic aging at birth. For example, pregnancy average PM10 exposure (per 10 unit increase) was associated with epigenetic age deceleration at birth (weeks) for both Knight and Bohlin clocks (β = −0.62, 95% CI: −1.17, −0.06; β = −0.32, 95% CI: −0.63, −0.01, respectively). Weekly DLMs revealed that increasing PM2.5 during the first trimester and second trimester were associated with decelerated epigenetic aging and that increasing PM10 during the preconception period was associated with decelerated epigenetic aging, using the Bohlin clock estimate. Prenatal ambient air pollution exposure, particularly in early and mid-pregnancy, was associated with decelerated epigenetic aging at birth.

Greenspace, stress, and health: how is epigenetics involved?

“…Epigenetic responses, including DNA methylation changes and epigenetic aging, to environmental exposures such as air pollution may occur as early as in utero and can have risks as severe as mortality (13,14). Prenatal ambient air pollution exposure has been found to be associated with epigenetic aging at birth, with long term implications for health (15). Such findings further indicate the importance of time course considerations regarding other environmental exposures associated with greenspace and how epigenetic responses mediate resultant health outcomes.…”

Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts

“…We have shown that DNAm clock, while universal in its foundational concept, can exhibit specific patterns and variations when analyzed across different ethnic groups. Factors contributing to these disparities might range from genetic backgrounds to varied environmental and socio-cultural practices that might not be readily available, such as alcohol consumption [ 34 , 104 ] and air pollution [ 105 , 106 ], both are known to alter epigenetics. These discrepancies, while enriching our understanding of epigenetic variability between ethnic groups, also serve as a clarion call for tailored healthcare and research approaches across populations.…”

Investigating the Potential Impact of Air Pollution on Alzheimer’s Disease and the Utility of Multidimensional Imaging for Early Detection

“…Environmental exposure and traffic-related exposure in children and the adult population have been found to modify DNA methylation essential for maintaining genomic integrity and regulating gene function. − Air pollutants target both the respiratory tract and brain through the olfactory axis, leading to microglial activation and the action of cytotoxic molecules in neuroinflammation and cell death . In fact, studies on animals using diesel exhaust with high levels of ultrafine particles have demonstrated that oxidative stress, protein misfolding, and plaques all contribute to the link between black carbon (pollutant and PM) and Alzheimer’s disease. − It is believed that the gas, particles, or material desorbed from the particle surface act to trigger inflammatory reactions, microglial activation, the generation of reactive oxygen species, and enhanced production and deposition of Aβ peptides when inhaled through the respiratory tract .…”