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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.

Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci.Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database.Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10–29, maternal blood early pregnancy P = 6.1 × 10–27, maternal blood late pregnancy P = 2.8 × 10–16, maternal placenta P = 5.6 × 10–15, fetal placenta P = 1.3 × 10–20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes.Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.