The association of prenatal ambient air pollution with placental epigenetic gestational age at birth.

BACKGROUND

Prenatal air pollutants have been associated with adverse birth outcomes, and DNA methylation (DNAm) changes in placenta may contribute to these associations. DNAm-based epigenetic gestational age (GA) estimators are emerging biomarkers for aging/biological age that can reflect early-life exposures and predict long-term health outcomes. We leveraged 103 mother-offspring pairs from the Early Autism Risk Longitudinal Investigation cohort to assess associations between prenatal air pollution and placental epigenetic GA at birth.

METHODS

Prenatal air pollution concentrations (NO, O, PM, and PM) were estimated from weekly data from monitoring stations near maternal residence and calculated for preconception and pregnancy periods. DNAm from fetal-side placenta samples was measured on Illumina HumanMethylation450 BeadChip. Epigenetic GA was computed using Lee's robust placenta clock algorithm. GA acceleration/deceleration was the residual of predicted epigenetic GA on chronologic GA, adjusted (intrinsic) or unadjusted (extrinsic) for cell type proportions. We used linear regressions to examine associations between average air pollution levels in each period and GA acceleration/deceleration, and weekly distributed lag models to examine critical exposure windows.

RESULTS

Higher pregnancy average O and PM exposures were associated with decelerated intrinsic (β = -0.65 and -0.79) and extrinsic GA (β = -0.69 and -0.74) at birth (per 10-unit increment). Trimester-specific analyses revealed higher O and PM exposures in trimesters 2 to 3 associated with decelerated GA at birth. Weekly distributed lag models suggested pregnancy weeks 21 to 31 and 21 to 29 were critical windows of O and PM exposures, respectively.

CONCLUSIONS

Prenatal air pollution exposures, especially during mid- to late-pregnancy, were associated with lower biological maturity at birth.